Name: 4721-98-6|6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline|97%
Brand: Ambeed
SKU: A706517
Price: 48.0 USD
Availability: InStock
Rating: 98 (27 reviews)

1
[ 4721-98-6 ]
[ 108-24-7 ]
[ 57621-04-2 ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine In dichloromethane at 60℃; for 3h;	Procedure for preparation of 1-(6,7-dimethoxy-1-methylene-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (6) (CAS Number: 57621-04-2) To a round-bottomed flask were added 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (9) (2.5 mmol, 513 mg) and a mixture of pyridine and acetic anhydride (1:1) (3.6 mL). The round-bottomed flask was capped with a rubber septum and the mixture was stirred at 60 °C for 3 h. Afterwards, the reaction mixture was cooled to room temperature and diluted with dichloromethane (15 mL). The mixture was washed with distilled water (15 mL) and with a 10% (w/v) aqueous solution of NaHCO3 (2 x 15 mL). The organic phase was dried over MgSO4. The residue was purified by column chromatography on silica gel using ethyl acetate as eluent to afford the desired product 6. Yield: 543 mg (88%); off-white solid; m.p. 100-101 oC (lit.15 m.p. 106-107 oC); Rf = 0.48 (eluent: ethyl acetate). 1H NMR (300 MHz, CDCl3): δ 7.08 (s, 1H), 6.59 (s, 1H), 5.60 (s, 1H), 4.97 (s, 1H), 3.98 (t, J = 6.0 Hz, 2H), 3.91 (s, 3H), 3.88 (s, 3H), 2.83 (t, J = 6.0 Hz, 2H), 2.23 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 169.3, 149.7, 147.6, 143.1, 127.9, 123.6, 111.1, 106.6, 104.2, 55.9, 55.8, 41.6, 28.5, 22.3; IR (KBr, cm-1): 3070.7, 2933.7, 1624.1, 1512.2, 1448.5, 1288.5, 974.1, 896.9; GC/MS (m/z, %): 247 (94.7), 232 (10.7), 219 (1.3), 204 (100.0), 190 (44.5) 174 (22.5).

Reference： [1]Corrêa, Bianca K.; Silva, Tamiris R.C.; Raminelli, Cristiano [Tetrahedron Letters, 2018, vol. 59, # 39, p. 3583 - 3585]
[2]Brossi,A. et al. [Helvetica Chimica Acta, 1960, vol. 43, p. 1459 - 1472] Brossi et al. [Chimia, 1958, vol. 12, p. 114]

2
[ 4721-98-6 ]
[ 4594-02-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	In tetralin at 190℃; for 2h;
75%	With Phenetole for 1h; Heating;
	With palladium at 180℃;

	With palladium on activated charcoal; 4-methylisopropylbenzene
	In various solvent(s) at 176℃; for 30h;
	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline In tetralin at 0℃; for 3h; Heating / reflux; Stage #2: With hydrogenchloride In tetralin; water at 20℃; Stage #3: With sodium hydroxide In water	2.3 Step 3.; Into a 1000 mL 3-necked round bottom flask' purged and maintained with an inert atmosphere of nitrogen while cooling in an ice bath at 0 0C was added 6,7- dimethoxy-l-methyl-3,4-dihydroisoquinoline (8 g, 39.02 mmol), 1,2,3,4- tetrahydronaphthalene (650 mL) and Pd/C (8 g). The reaction mixture was then refluxed for 3 hr. The reaction was monitored by TLC (EtOAc/MeOH (10:1, v/v)). Upon completion, the reaction mixture was cooled to room temperature, and filtered. The pH was adjusted to 2 by the addition of 10% aqueous HCl. The aqueous layer was separated and the pH was adjusted to 10 by the addition of 10% aqueous NaOH. The resulting solution was extracted with EtOAc, and the organic fraction was dried over anhydrous Na2SO4 and concentrated to provide 6,7-dimethoxy-l-methylisoquinoline as a brown solid (7 g).

Reference： [1]Mahboobi; Seidl; Eibler; Wiegrebe [Archiv der Pharmazie, 1992, vol. 325, # 10, p. 679 - 683]
[2]Postaire, E.; Martinez, D.; Viel, C.; Chastagnier, M.; Hamon, M. [Bulletin de la Societe Chimique de France, 1988, # 6, p. 982 - 988]
[3]Spaeth; Polgar [Monatshefte fur Chemie, 1929, vol. 51, p. 199]
[4]Walker [Journal of the American Chemical Society, 1954, vol. 76, p. 3999,4001]
[5]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]
[6]Current Patent Assignee: AMGEN INC - WO2007/103554, 2007, A1 Location in patent: Page/Page column 57-58

3
[ 4721-98-6 ]
(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline With triethylsilane; [Cr(CO)3((CH₃)2NC₆H₃C₅H₄N)IrCl(C₅(CH₃)5)] In methanol at 25℃; for 3h; Inert atmosphere; Stage #2: With water In methanol Inert atmosphere;
100%	With indium; ammonium chloride In ethanol Heating;
99%	With sodium tetrahydroborate; toluene-4-sulfonic acid at 25℃;

98%	With hydrogen In methanol for 24h;
98%	With formic acid; C₂₉H₃₂ClIrNO; sodium formate In water for 16h;
96%	With hydrogen In ethanol at 29℃; for 0.333333h;
94%	With butyl triphenylphosphonium tetraborate at 20℃; for 0.1h;
92%	With borane-ammonia complex; pyrrolidine(borane); [RuCl₂(2-diphenylphosphinoethylamine)₂]; potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;
90%	With 1-benzyl-1-azonia-4-azabicyclo[2.2.2]octane tetrahydroborate In <i>tert</i>-butyl alcohol at 20℃; for 0.3h;
85%	With benzyltriphenylphosphonium borohydride In methanol at 20℃; for 0.416667h;
84%	With sodium tetrahydroborate In methanol at 0 - 20℃;
74%	With sodium tetrahydroborate In water; isopropyl alcohol at 0 - 20℃; for 5h;	Procedure for preparation of 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (5) (CAS Number: 5784-74-7)⁶ To a round-bottomed flask were added sodium borohydride (5 mmol, 189 mg) and a mixture of distilled water and isopropanol (1:1) (10 mL). The mixture was cooled to 0 oC under stirring. After that, a solution of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (9) (5 mmol, 1.03 g) in isopropanol (2.5 mL) was added dropwise using syringe and needle. The mixture was maintained under stirring at room temperature for 5 h. Afterwards, a 10% (w/v) aqueous solution of HCl was added dropwise to the mixture until pH 3. Then, a 10% (w/v) aqueous solution of NaOH was added dropwise until pH 10. The reaction was extracted with CH2Cl2 (3 x 50 mL) and dried over MgSO4. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using methanol as eluent, affording the desired product 5. Yield: 766 mg (74%); off-white solid; m.p. 49-51 oC (m.p. lit.6b 47-49 oC); Rf = 0.20 (eluent: methanol); 1H NMR (300 MHz, CDCl3): δ 6.63 (s, 1H), 6.57 (s, 1H), 4.05 (q, J = 6.8 Hz, 1H), 3.85 (s, 6H), 3.25 (dt, J = 12.5, 5.1 Hz, 1H), 2.99 (ddd, J = 12.8, 8.3, 4.6 Hz, 1H), 2.79 (ddd, J = 15.5, 8.9, 6.1 Hz, 1H), 2.65 (dt, J = 16.1, 4.7 Hz, 1H), 1.98 (s, 1H), 1.44 (d, J = 6.6 Hz); 13C NMR (75 MHz, CDCl3,): δ 147.3, 147.2, 132.3, 126.7, 111.7, 109.0, 55.9, 55.8, 51.2, 41.7, 29.4, 22.8; IR (KBr, cm-1): 3421.7, 3271.3, 2958.8, 2929.9, 1514.1, 1462.0, 1255.7, 1222.9, 1029.9; GC/MS (m/z, %): 207 (5.9), 192 (100.0) 176 (14.0), 148 (11.4), 131 (6.0).
73%	With sodium tetrahydroborate In water; isopropyl alcohol at 0℃; for 5h;
36%	With magnesium(II) perchlorate; pyrrolo<2,3-b>pyridine derivative In acetonitrile at 60℃; for 72h; reactions of derivatives;
36%	With magnesium(II) perchlorate; pyrrolo<2,3-b>pyridine derivative In acetonitrile at 60℃; for 72h;
	With ethanol; ammonia; nickel at 100℃; Hydrogenation;
	With ethanol; nickel-copper-cobalt mixed catalyst at 80℃; Hydrogenation;
	With methanol; Pd/SrCO₃ Hydrogenation_.bei Raumtemperatur;
	With methanol; palladium; acetic acid at 40 - 50℃; Hydrogenation;
	With methanol; platinum
	With hydrogenchloride; water; zinc Reagens 4:Kupfer(II)-sulfat;
	With hydrogen In ethanol Ambient temperature;
90 % Spectr.	With isopropyl alcohol at 85℃; for 18h;
	With sodium tetrahydroborate In methanol
	With sodium tetrahydroborate In ethanol
79 % ee	With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 65℃; for 68.5h;
76 % ee	With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 80℃; for 68.5h;
	With formic acid/triethylamine complex 5:2; Cp*Rh(TsNC₆H₄NH) In d⁽⁴⁾-methanol at 26.84℃;
	With sodium tetrahydroborate In methanol at 20℃; for 1h;
	With formic acid; N-[(1R,2R)-2-(dimethylamino)-1,2-diphenylethyl]-4-methylbenzenesulfonamide benzene ruthenium chloride; triethylamine In methanol at 30℃; for 72h; Inert atmosphere;
	With [η⁵η5-(biot-2-(2,3,4,5-tetramethylcyclopentadienyl)ethylamine)IrCl₂]₂; sodium formate In aq. buffer at 55℃; Schlenk technique; Inert atmosphere;
	With C₂₂H₂₈ClIrN₃O₂S⁽¹⁺⁾*Cl^(1-); sodium formate In dimethyl sulfoxide at 4℃; for 44h;
	With maleiimide; Cp*Ir(biot-p-L)Cl; sodium formate In N,N-dimethyl-formamide at 20℃; for 48h;
	With Cp*Ir(biot-p-L)Cl In aq. buffer at 25℃;
	With formic acid; C₃₁H₃₆ClN₂O₂RhS; triethylamine In methanol; water at 40℃; for 0.1h;
	With Cp*Ir(biot-p-L)Cl; sodium formate; streptavidin In aq. buffer at 20℃; for 4.5h;
	With potassium borohydride In methanol at 20℃; for 5.33333h;
	With sodium tetrahydroborate In methanol at 20℃;	84.1 Preparation of 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Sodium borohydride was added in small portions to a methanol solution (15 ml) of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (5.61 mmol) at room temperature for 20-30 minutes. The reaction mixture was then stirred for 3-4 hours. After the reaction was terminated (TLC EA: hexane = 3: 7), the solvent was distilled off and 10 ml of water + conc. 5 ml of HCl were added to the reaction mixture. After that, the reaction mixture was extracted with methylene chloride. The aqueous layer was basified with 1N KOH and extracted with ethyl acetate. The solvent was evaporated to give a dark yellow residue which was used in the next step without purification.
	With C₂₂H₃₄ClIrN₄O₃S In aq. buffer at 20℃; for 48h;
	With sodium tetrahydroborate In methanol at 20℃;	84.1 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Sodium borohydride was added to the methanol solution (15 ml) of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (5.61 mmol) at room temperature for 20-30 minutes in small portions. The reaction mixture was then stirred for 3-4 hours. After the reaction is complete (TLC EA: hexane = 3: 7), the solvent is distilled off and 10 ml of water + conc. 5 ml of HCl were added to the reaction mixture. After that, the reaction mixture was extracted with methylene chloride. The aqueous layer was basified with 1N KOH and extracted with ethyl acetate. The solvent was evaporated to give a dark yellow residue which was used in the next step without purification.
	With Cp*Ir(biot-p-L)Cl In aq. buffer at 37℃; for 48h; Sealed tube;
	With sodium formate In aq. phosphate buffer at 80℃; for 4h; Sonication; Inert atmosphere; Schlenk technique;
	With Cp*Ir(biot-p-L)Cl; sodium formate; sodium hydroxide In aq. buffer at 37℃; for 48h;
	With [Cp*Ir(biot-p-L)Cl] In dimethyl sulfoxide at 25℃; for 16h;
	With 3-(N-morpholino)propanesulfonic acid; C-(1-methyl-1H-imidazol-4-yl)methylamine; [η⁵η5-(biot-2-(2,3,4,5-tetramethylcyclopentadienyl)ethylamine)IrCl₂]₂; sodium formate In water at 30℃; for 18h;
	With Cp*Ir(biot-p-L)Cl In dimethyl sulfoxide at 25℃; for 24h; Sealed tube;
	With 3-(N-morpholino)propanesulfonic acid; vancomycin; [IrCp*((R)-2-((R)-2-(4-(N-(2-aminoethyl)sulfamoyl)benzamido)propanamido)propanoic acid)Cl]Cl In aq. buffer at 20℃; for 18h; enantioselective reaction;
	With formic acid; di-μ-iodo-(η⁵-N,N,-2,3,4,5-hexamethylcyclopenta-2,4-dienylcarboxamide)iridium(III) iodide dimer; triethylamine; (R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine In acetonitrile at 28℃; for 14h;

Reference： [1]Iali, Wissam; Paglia, Frederic La; Pfeffer, Michel; Djukic, Jean-Pierre; Goff, Xavier-Frederic Le; Sredojevic, Dusan [Chemical Communications, 2012, vol. 48, # 83, p. 10310 - 10312,3]
[2]Pitts; Harrison; Moody [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2001, # 9, p. 955 - 977]
[3]Byung, Tae Cho; Sang, Kyu Kang [Tetrahedron, 2005, vol. 61, # 24, p. 5725 - 5734]
[4]Leseche, Bernard; Gilbert, Jacques; Viel, Claude [Journal of Heterocyclic Chemistry, 1981, vol. 18, p. 143 - 153]
[5]Talwar, Dinesh; Li, Ho Yin; Durham, Emma; Xiao, Jianliang [Chemistry - A European Journal, 2015, vol. 21, # 14, p. 5370 - 5379]
[6]Fujii, Tozo; Yamada, Koichiro; Minami, Shinzaburo; Yoshifuji, Shigeyuki; Ohba, Masashi [Chemical and pharmaceutical bulletin, 1983, vol. 31, # 8, p. 2583 - 2592]
[7]Hajipour; Mohammadpoor-Baltork; Noroallhi [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 2, p. 152 - 156]
[8]Blaquiere, Nicole; Diallo-Garcia, Sarah; Gorelsky, Serge I.; Black, Daniel A.; Fagnou, Keith [Journal of the American Chemical Society, 2008, vol. 130, # 43, p. 14034 - 14035]
[9]Hajipour; Mohammadpoor-Baltork; Rahi [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2000, vol. 39, # 3, p. 239 - 242]
[10]Hajipour; Mallakpour; Najafi [Phosphorus, Sulfur and Silicon and the Related Elements, 2001, vol. 170, p. 197 - 203]
[11]Kwan, Maria H. T.; Breen, Jessica; Bowden, Martin; Conway, Louis; Crossley, Ben; Jones, Martin F.; Munday, Rachel; Pokar, Nisha P. B.; Screen, Thomas; Blacker, A. John [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2458 - 2473]
[12]Corrêa, Bianca K.; Silva, Tamiris R.C.; Raminelli, Cristiano [Tetrahedron Letters, 2018, vol. 59, # 39, p. 3583 - 3585]
[13]Schonenberger; Brossi [Helvetica Chimica Acta, 1986, vol. 69, # 6, p. 1486 - 1497]
[14]Leroy, Corine; Dupas, Georges; Bourguignon, Jean; Queguiner, Guy [Tetrahedron, 1994, vol. 50, # 46, p. 13135 - 13144]
[15]Leroy, Corine; Dupas, Georges; Bourguignon, Jean; Queguiner, Guy [Tetrahedron, 1994, vol. 50, # 46, p. 13135 - 13144]
[16]Barbier; Rumpf [Bulletin de la Societe Chimique de France, 1953, p. 293,295]
[17]Fries; Bestian [Justus Liebigs Annalen der Chemie, 1938, vol. 533, p. 72,83]
[18]Osbond [Journal of the Chemical Society, 1951, p. 3464,3469]
[19]Spaeth; Dengel [Chemische Berichte, 1938, vol. 71, p. 113,117]
[20]Schoepf; Bayerle [Justus Liebigs Annalen der Chemie, 1934, vol. 513, p. 190,193,200]
[21]Spaeth; Dengel [Chemische Berichte, 1938, vol. 71, p. 113,117]
[22]Hocquaux; Viel; Brunaud; et al. [European Journal of Medicinal Chemistry, 1983, vol. 18, # 4, p. 331 - 338]
[23]Mizushima, Eiichiro; Yamaguchi, Motowo; Yamagishi, Takamichi [Chemistry Letters, 1997, # 3, p. 237 - 238]
[24]Voskressensky, Leonid G.; Listratova, Anna V.; Borisova, Tatiana N.; Alexandrov, Grigoriy G.; Varlamov, Alexey V. [European Journal of Organic Chemistry, 2007, # 36, p. 6106 - 6117]
[25]Mrsic, Natasa; Minnaard, Adriaan J.; Feringa, Ben L.; Vries, Johannes G. de [Journal of the American Chemical Society, 2009, vol. 131, p. 8358 - 8359]
[26]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2002/8169, 2002, A1 Location in patent: Table Row1
[27]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2002/8169, 2002, A1 Location in patent: Table Row2
[28]Location in patent: scheme or table Blacker, A. John; Clot, Eric; Duckett, Simon B.; Eisenstein, Odile; Grace, Jake; Nova, Ainara; Perutz, Robin N.; Taylor, David J.; Whitwood, Adrian C. [Chemical Communications, 2009, # 44, p. 6801 - 6803]
[29]Evanno, Laurent; Ormala, Joel; Pihko, Petri M. [Chemistry - A European Journal, 2009, vol. 15, # 47, p. 12963 - 12967]
[30]Soni, Rina; Cheung, Fung Kei; Clarkson, Guy C.; Martins, Jose E. D.; Graham, Mark A.; Wills, Martin [Organic and Biomolecular Chemistry, 2011, vol. 9, # 9, p. 3290 - 3294]
[31]Zimbron, Jeremy M.; Heinisch, Tillmann; Schmid, Maurus; Hamels, Didier; Nogueira, Elisa S.; Schirmer, Tilman; Ward, Thomas R. [Journal of the American Chemical Society, 2013, vol. 135, # 14, p. 5384 - 5388]
[32]Monnard, Fabien W.; Nogueira, Elisa S.; Heinisch, Tillmann; Schirmer, Tilman; Ward, Thomas R. [Chemical Science, 2013, vol. 4, # 8, p. 3269 - 3274]
[33]Wilson, Yvonne M.; Dürrenberger, Marc; Nogueira, Elisa S.; Ward, Thomas R. [Journal of the American Chemical Society, 2014, vol. 136, # 25, p. 8928 - 8932]
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[38]Current Patent Assignee: CHUNGNAM NATIONAL UNIVERSITY - KR2016/108281, 2016, A Location in patent: Paragraph 0777-0779
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4
[ 6275-29-2 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With trichlorophosphate In toluene at 40℃; for 3h; Molecular sieve; Reflux;
90%	With 1-ethyl-3-methylimidazolium triflate; trichlorophosphate at 95 - 100℃; for 3h; Inert atmosphere;	6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline 2a General procedure: General procedure for the preparation of 3,4-dihydroisoquinolines 2 in ILs. A mixture of N-acyl-2-arylethylamine 1 (1 mmol), POCl3 (2.5 or 9 mmol) and 2 g of the corresponding IL (Table 1) was heated with a backflow condenser and protection from moisture at 95-100 °C at stirring until the full consumption of 1 (TLC control). Then the reaction mixture was cooled to 20 °C, diluted with water (3 ml) and NaOH aqueous solution was added dropwise to pH 10. The liberated 3,4-dihydroisoquinoline was extracted with diethyl ether (5 × 3 ml), the ether solution was washed with water (2 × 3 ml), dried with MgSO4 and the solvent was evaporated. The residue was purified by flash chromatography through a short column with SiO2 or by crystallization.
90%	Stage #1: N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide With trichlorophosphate In toluene at 40℃; for 2h; Reflux; Stage #2: With sodium hydroxide In water at 20℃; for 0.166667h;

90%	With trichlorophosphate In o-xylene for 3h; Cooling with ice; Reflux;
87%	With trichlorophosphate
87%	With 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate; trichlorophosphate at 90 - 100℃; for 1h;
85.8%	With trichlorophosphate In o-xylene for 3h; Reflux;
80%	With trichlorophosphate In toluene Heating;
80%	With trichlorophosphate In benzene Heating;
80%	With triphenyl phosphite; bromine; triethylamine In dichloromethane at -60 - 20℃;
76%	With trichlorophosphate In toluene for 2.5h; Heating;
74%	With trichlorophosphate In toluene for 2h; Heating;
74%	With PPA In toluene for 10h; Reflux;
72%	With trichlorophosphate In toluene Heating;
68%	With trichlorophosphate In 5,5-dimethyl-1,3-cyclohexadiene at 160℃; for 3h; Inert atmosphere;
64%	With trichlorophosphate In toluene for 1h; Heating;
58%	With trichlorophosphate for 18h;
	With phosphorus pentaoxide; toluene
	With toluene; trichlorophosphate at 130℃;
	With pyridine; phosphorus pentoxide
	With trichlorophosphate
	With trichlorophosphate In toluene Heating;
	Multi-step reaction with 2 steps 1: 51 percent / AlCl₃ / nitrobenzene / 2.5 h / 35 °C 2: 96 percent / 1N HCl / 18 h / Heating
	Multi-step reaction with 3 steps 1: CH₂Cl₂ / 0.5 h / Ambient temperature 2: FeCl₃ / CH₂Cl₂ / -10 deg C to rt 3: conc. H₂SO₄ / methanol / Heating
	With trichlorophosphate
	With trichlorophosphate In toluene
	With trichlorophosphate In toluene for 2h; Reflux;
	Stage #1: N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide With trichlorophosphate In toluene at 120℃; for 3.5h; Stage #2: With sodium hydroxide In water at 20℃;	2.2 Step 2.; A mixture of N-(3s4-dimethoxyphenethyl)acetamide (25 g, 112.11 mmol) and POCl3 (37 mL) in toluene (187 mL) was stirred at 120 0C for 3.5 hr. The reaction was monitored by TLC (EtOAc: PE (1 :1, v/v)). Upon completion, the reaction mixture was cooled to room temperature and the pH was adjusted to 12 by the addition of NaOH (4N). The resulting mixture was washed with EtOAc and filtration was performed to yield 6,7- dimethoxy-l-methyl-3,4-dihydroisoquinoline as a yellow solid (20 g).
	Multi-step reaction with 2 steps 1: trichlorophosphate / toluene / 2 h / 20 - 111 °C / Inert atmosphere 2: potassium carbonate; sodium chloride / dichloromethane / Inert atmosphere
	With trichlorophosphate In acetonitrile for 1h; Reflux; Inert atmosphere;	4.1.1.1 6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline (1a) A solution of 3,4-dimethoxyphenethylamine (1g, 5.52mmol) in dry Ac2O (10mL) and pyridine (0.5mL) was stirred under nitrogen atmosphere at room temperature for 3h. Then, the reaction mixture was diluted with water (15mL) and extracted with CH2Cl2. The combined organic phases were dried over Na2SO4 and evaporated to dryness to give 1.02g (81%) of 1 as a white solid, which was used in the next step with no further purification. Next, a solution of N-(3,4-dimethoxyphenethyl)acetamide 1 (500mg, 2.24mmol) in dry CH3CN (20mL) was treated with POCl3 (0.37mL, 4.1mmol) and refluxed for 1h in a nitrogen atmosphere. The reaction mixture was concentrated to dryness, re-dissolved in water and basified with NH4OH until pH=9. The mixture was extracted with CH2Cl2. The organic solution was dried over Na2SO4 and evaporated to dryness to give 312mg of 1a (67%) which was used in the next step with no further purification. Characterization data for 1 and 1a were in agreement with published data [35].
	With toluene; trichlorophosphate at 130℃;
	With trichlorophosphate In ethyl acetate for 6h; Reflux; Inert atmosphere;
100 %Spectr.	With phenylsilane; 1-bromo-1,2,2,3,4,4-pentamethylphosphetanium bromide; Diethyl 2-bromomalonate In 1,2-dichloro-ethane at 80℃; for 0.75h; Sealed tube; Inert atmosphere; Glovebox;
	Multi-step reaction with 2 steps 1: trichlorophosphate / toluene / 2 h / 40 °C / Inert atmosphere; Reflux 2: sodium hydroxide / water / 0.17 h / 20 °C
	With 2-chloropyridine; trifluoromethylsulfonic anhydride In dichloromethane at -78℃; Inert atmosphere;
	With polyphosphoric acid

Reference： [1]Kwan, Maria H. T.; Breen, Jessica; Bowden, Martin; Conway, Louis; Crossley, Ben; Jones, Martin F.; Munday, Rachel; Pokar, Nisha P. B.; Screen, Thomas; Blacker, A. John [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2458 - 2473]
[2]Epishina, Margarita A.; Kulikov, Alexander S.; Struchkova, Marina I.; Ignat'Ev, Nikolai V.; Schulte, Michael; Makhova, Nina N. [Mendeleev Communications, 2012, vol. 22, # 5, p. 267 - 269]
[3]Rossini, Allan F. C.; Muraca, Ana Carolina A.; Casagrande, Gleison A.; Raminelli, Cristiano [Journal of Organic Chemistry, 2015, vol. 80, # 20, p. 10033 - 10040]
[4]Hanusek, Jiří; Mwansa, Joseph M.; Page, Michael I.; Stirling, Matthew J.; Sweeney, Gemma; Váňa, Jiří [Dalton Transactions, 2022, vol. 51, # 7, p. 2696 - 2707]
[5]Postaire, E.; Martinez, D.; Viel, C.; Chastagnier, M.; Hamon, M. [Bulletin de la Societe Chimique de France, 1988, # 6, p. 982 - 988]
[6]Judeh, Zaher M.A.; Ching, Chi Bun; Bu, Jie; McCluskey, Adam [Tetrahedron Letters, 2002, vol. 43, # 29, p. 5089 - 5091]
[7]Stirling, Matthew J.; Mwansa, Joseph M.; Sweeney, Gemma; Blacker, A. John; Page, Michael I. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 7092 - 7098]
[8]Leseche, Bernard; Gilbert, Jacques; Viel, Claude [Journal of Heterocyclic Chemistry, 1981, vol. 18, p. 143 - 153]
[9]Hocquaux; Viel; Brunaud; et al. [European Journal of Medicinal Chemistry, 1983, vol. 18, # 4, p. 331 - 338]
[10]Location in patent: scheme or table Vaccari, Daniele; Davoli, Paolo; Ori, Claudia; Spaggiari, Alberto; Prati, Fabio [Synlett, 2008, # 18, p. 2807 - 2810]
[11]Bremner; Coban; Griffith; Groenewoud; Yates [Bioorganic and medicinal chemistry, 2000, vol. 8, # 1, p. 201 - 214]
[12]Zhang, Fa; Dryhurst, Glenn [Journal of Medicinal Chemistry, 1993, vol. 36, # 1, p. 11 - 20]
[13]Location in patent: scheme or table Jacobs, Jan; Van, Tuyen Nguyen; Stevens, Christian V.; Markusse, Peter; De Cooman, Paul; Maat, Leendert; De Kimpe, Norbert [Tetrahedron Letters, 2009, vol. 50, # 26, p. 3698 - 3701]
[14]Zhao, Bao-Xiang; Yu, Yang; Eguchi, Shoji [Organic Preparations and Procedures International, 1997, vol. 29, # 2, p. 185 - 194]
[15]Vaclavik, Jiri; Pechacek, Jan; Vilhanova, Beata; Sot, Petr; Januscak, Jakub; Matousek, Vaclav; Prech, Jan; Bartova, Simona; Kuzma, Marek; Kacer, Petr [Catalysis Letters, 2013, vol. 143, # 6, p. 555 - 562]
[16]Glusa; Gruner; Hagen; Lohmann; Foken [Pharmazie, 1990, vol. 45, # 6, p. 408 - 410]
[17]Pitts; Harrison; Moody [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2001, # 9, p. 955 - 977]
[18]Spaeth; Polgar [Monatshefte fur Chemie, 1929, vol. 51, p. 199]
[19]Barbier; Rumpf [Bulletin de la Societe Chimique de France, 1953, p. 293,295] Walker [Journal of the American Chemical Society, 1954, vol. 76, p. 3999,4001]
[20]Itoh; Sugasawa [Tetrahedron, 1957, vol. 1, p. 45,48]
[21]Gulyakevich; Kurman; Mikhal'chuk [Russian Journal of Organic Chemistry, 2005, vol. 41, # 12, p. 1806 - 1809]
[22]Gibson, Harry W.; Berg, Michael A. G.; Dickson, Jennifer Clifton; Lecavalier, Pierre R.; Wang, Hong; Merola, Joseph S. [Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5759 - 5770]
[23]Orito, Kazuhiko; Matsuzaki, Tsutomu; Suginome, Hiroshi; Rodrigo, Russel [Heterocycles, 1988, vol. 27, # 10, p. 2403 - 2412]
[24]Larsen, Robert D.; Reamer, Robert A.; Corley, Edward G.; Davis, Paul; Grabowski, Edward J. J.; et al. [Journal of Organic Chemistry, 1991, vol. 56, # 21, p. 6034 - 6038]
[25]Voskressensky, Leonid G.; Listratova, Anna V.; Borisova, Tatiana N.; Alexandrov, Grigoriy G.; Varlamov, Alexey V. [European Journal of Organic Chemistry, 2007, # 36, p. 6106 - 6117]
[26]Location in patent: scheme or table Lee, Chih-Shone; Yu, Tsung-Ching; Luo, Jian-Wen; Cheng, Yen-Yao; Chuang, Che-Ping [Tetrahedron Letters, 2009, vol. 50, # 31, p. 4558 - 4562]
[27]Evanno, Laurent; Ormala, Joel; Pihko, Petri M. [Chemistry - A European Journal, 2009, vol. 15, # 47, p. 12963 - 12967]
[28]Current Patent Assignee: AMGEN INC - WO2007/103554, 2007, A1 Location in patent: Page/Page column 57
[29]Soni, Rina; Cheung, Fung Kei; Clarkson, Guy C.; Martins, Jose E. D.; Graham, Mark A.; Wills, Martin [Organic and Biomolecular Chemistry, 2011, vol. 9, # 9, p. 3290 - 3294]
[30]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]
[31]Anthony-Barbier [1954, vol. 6, p. 319,336]
[32]Zhu, Ruiheng; Xu, Zhangli; Ding, Wei; Liu, Shiling; Shi, Xiaoxin; Lu, Xia [Chinese Journal of Chemistry, 2014, vol. 32, # 10, p. 1039 - 1048]
[33]Lecomte, Morgan; Lipshultz, Jeffrey M.; Kim-Lee, Shin-Ho; Li, Gen; Radosevich, Alexander T. [Journal of the American Chemical Society, 2019, vol. 141, # 32, p. 12507 - 12512]
[34]Casagrande, Gleison A.; Deflon, Victor M.; Martins, Gabriel R.; Oliveira-Silva, Diogo; Perecim, Givago P.; Pinto, Leandro M. C.; Raminelli, Cristiano [Tetrahedron, 2020]
[35]Barrios-Rivera, Jonathan; Xu, Yingjian; Wills, Martin [Organic Letters, 2020, vol. 22, # 16, p. 6283 - 6287]
[36]Mitachi, Katsuhiko; Salinas, Yandira G.; Connelly, Michele; Jensen, Nicholas; Ling, Taotao; Rivas, Fatima [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 14, p. 4536 - 4539]

5
[ 79-37-8 ]
[ 4721-98-6 ]
[ 102421-38-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine In 1,2-dimethoxyethane at 0℃; for 0.25h;

Reference： [1]Saa, Carlos; Guitian, Enrique; Castedo, Luis; Suau, Rafael; Saa, Jose Manuel [Journal of Organic Chemistry, 1986, vol. 51, # 14, p. 2781 - 2784]

6
[ 4721-98-6 ]
[ 7154-66-7 ]
[ 49619-30-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine In dichloromethane
	With triethylamine
	With TEA In dichloromethane Ambient temperature;

Reference： [1]Location in patent: scheme or table Lee, Chih-Shone; Yu, Tsung-Ching; Luo, Jian-Wen; Cheng, Yen-Yao; Chuang, Che-Ping [Tetrahedron Letters, 2009, vol. 50, # 31, p. 4558 - 4562]
[2]Takano; Suzuki; Kijima; Ogasawara [Tetrahedron Letters, 1990, vol. 31, # 16, p. 2315 - 2318]
[3]Bombrun, Agnes; Sageot, Olivia [Tetrahedron Letters, 1997, vol. 38, # 6, p. 1057 - 1060]

7
[ 4721-98-6 ]
[ 407-25-0 ]
[ 101064-78-2 ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine In dichloromethane at -50℃; for 3h; Inert atmosphere;
70%	With pyridine for 0.5h; Ambient temperature;
70%	With pyridine In dichloromethane at -50℃; for 3h; Inert atmosphere;

69%

With pyridine In dichloromethane at -50℃; for 3h;

Reference： [1]Achary, Raghavendra; Mathi, Gangadhar Rao; Kim, Seulgi; Hwang, Jong Yeon; Kim, Pilho [Organic and Biomolecular Chemistry, 2018, vol. 16, # 9, p. 1452 - 1456]
[2]Atanes, N.; Castedo, L.; Guitian, E.; Saa, C.; Saa, J. M.; Suau, R. [Journal of Organic Chemistry, 1991, vol. 56, # 9, p. 2984 - 2988]
[3]Rossini, Allan F. C.; Muraca, Ana Carolina A.; Casagrande, Gleison A.; Raminelli, Cristiano [Journal of Organic Chemistry, 2015, vol. 80, # 20, p. 10033 - 10040]
[4]Leroy, Corine; Dupas, Georges; Bourguignon, Jean; Queguiner, Guy [Tetrahedron, 1994, vol. 50, # 46, p. 13135 - 13144]

8
[ 4721-98-6 ]
[ 74-88-4 ]
[ 17104-28-8 ]

Yield	Reaction Conditions	Operation in experiment
96%	In butanone for 9h; Heating;
95%	In acetone	Preparation of N-Methyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinium iodide Preparation of N-Methyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinium iodide To a stirred solution of 1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline in acetone was added methyl iodide and the reaction mixture was stirred at room temperature for 16 hours. A bright yellow precipitate formed. The by-products and methyl iodide were removed in vacuo to afford the desired compound in 95% yield.
75%	In methanol; acetone for 0.5h; Heating;

In N,N-dimethyl-formamide for 0.75h; Heating; Yield given;

Reference： [1]Pitts; Harrison; Moody [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2001, # 9, p. 955 - 977]
[2]Current Patent Assignee: NPIL PHARMACEUTICALS UK - US6509467, 2003, B1
[3]Cui, Wenhua; Iwasa, Kinuko; Tokuda, Harukuni; Kashihara, Akiko; Mitani, Yosuke; Hasegawa, Tomoko; Nishiyama, Yumi; Moriyasu, Masataka; Nishino, Hoyoku; Hanaoka, Miyoji; Mukai, Chisato; Takeda, Kazuyoshi [Phytochemistry, 2006, vol. 67, # 1, p. 70 - 79]
[4]Barker, John M.; Huddleston, Patrick R.; Clephane, Janette; Wood, Michael L.; Holmes, David [Journal of the Chemical Society. Perkin transactions I, 1985, p. 275 - 282]

9
[ 4721-98-6 ]
[ 63283-42-1 ]

Yield	Reaction Conditions	Operation in experiment
90.9%	With hydrogen In methanol at 40℃;

Reference： [1]Glusa; Gruner; Hagen; Lohmann; Foken [Pharmazie, 1990, vol. 45, # 6, p. 408 - 410]

10
[ 4721-98-6 ]
[ 493-48-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With silver hexafluoroantimonate; C₃₁H₃₆ClN₂O₂RhS; hydrogen In dichloromethane; water at 20℃; for 4h; Autoclave; optical yield given as %ee; enantioselective reaction;
90%	With n-butyllithium; (R,R)-ethylene-1,2-bis(η⁵-4,5,6,7-tetrahydro-1-indenyl)zirconium dichloride (R)-1,1'-binaphth-2,2'-diolate; phenylsilane; hydrogen In tetrahydrofuran; hexane at 65℃; for 11h;
90%	With aluminum oxide; sodium tris[(S)-N,N-phthaloylleucine]borohydride

90%	With Noyori's catalyst; sodium formate; cetyltrimethylammonim bromide In water at 20℃; for 16h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
88%	With Noyori's catalyst; formic acid; triethylamine In acetonitrile at 30℃; Inert atmosphere;
84%	With formic acid; [Ru(η6-p-cymene)(HNC(Ph)C(Ph)NTs)]; triethylamine In acetonitrile at 28℃; for 2h;
82%	With (R,R,R)-bis(1-methyl-4,5,6,7-tetrahydroindene)titanium; hydrogen at 65℃;
82%	With formic acid; C₃₄H₃₃ClN₂O₂RuS; triethylamine In methanol at 28℃; for 4.5h; optical yield given as %ee; enantioselective reaction;
76%	With D-glucose; BmGDH; imine reductase from Stackebrandtia nassauensis; NADP In aq. phosphate buffer at 30℃; for 12h; Enzymatic reaction; enantioselective reaction;
	With formic acid; triethylamine In dichloromethane at 20℃; for 24h; optical yield given as %ee; enantioselective reaction;
	With formic acid; C₂₅H₂₉ClN₂O₃RuS; triethylamine at 30℃; for 20h; Inert atmosphere; enantioselective reaction;
>95 % ee	With formic acid; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; triethylamine; (R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine In methanol at 22.84℃; Inert atmosphere;
> 98 % ee	With D-glucose; (S)-imine reductase from Streptomyces sp. GF₃₅₄₆; NADPH In aq. phosphate buffer; N,N-dimethyl-formamide at 30℃; for 6h; Enzymatic reaction; enantioselective reaction;
99 % ee	With C₃₄H₃₉F₃N₂O₅RuS₂⁽¹⁺⁾; hydrogen at 25℃; Autoclave; Inert atmosphere; Ionic liquid; enantioselective reaction;
94 % ee	With formic acid; Noyori's catalyst; triethylamine In acetonitrile at 30℃;	General procedure for asymmetric transfer hydrogenation General procedure: The formic acid-triethylamine azeotropic mixture (218 μL; 6.3 eq of formic acid with respect to the imine) was charged into a round-bottom flask (10 mL), followed by the catalyst (0.01 eq) dissolved in acetonitrile (1 mL). The resulting mixture was stirred for 10 min to activate the catalyst. The imine (0.42 mmol) dissolved in acetonitrile (1 mL) was introduced at once and the mixture was stirred at 30 °C. The samples of the reaction mixture (60 μL) were collected at 10, 20, 30, 40, 50, 90, 120 and 180 min. (0014) Each sample was quenched by using saturated solution of Na2CO3 (1 mL) and extracted with diethyl ether (3 × 1 mL). Combined extracts were dried over anhydrous sodium sulfate and the solvent was stripped off in a stream of nitrogen. The dry sample was dissolved in acetonitrile (1 mL) and analyzed.
> 99 % ee	With alcohol dehydrogenase from Lactobacillus brevis; imine reductase from Streptomyces sp. GF₃₅₄₆; NADPH In aq. phosphate buffer; isopropyl alcohol at 30℃; for 24h; Enzymatic reaction; stereoselective reaction;
	Multi-step reaction with 3 steps 1: pyridine / dichloromethane / 3 h / 60 °C 2: hydrogen; Ru(OCOCH₃)2{(S)-2,2'-bis(diphenylphosphino)-1,1'-dinaphthyl)} / dichloromethane; ethanol / 72 h / 25 °C / 15201 Torr 3: lithium hydroxide monohydrate; water / ethanol / 1 h / 180 °C / Microwave irradiation

Reference： [1]Li, Chaoqun; Xiao, Jianliang [Journal of the American Chemical Society, 2008, vol. 130, # 40, p. 13208 - 13209]
[2]Willoughby, Christopher A.; Buchwald, Stephen L. [Journal of the American Chemical Society, 1994, vol. 116, # 20, p. 8952 - 8965]
[3]Hajipour; Hantehzadeh [Journal of Organic Chemistry, 1999, vol. 64, # 23, p. 8475 - 8478]
[4]Evanno, Laurent; Ormala, Joel; Pihko, Petri M. [Chemistry - A European Journal, 2009, vol. 15, # 47, p. 12963 - 12967]
[5]Kwan, Maria H. T.; Breen, Jessica; Bowden, Martin; Conway, Louis; Crossley, Ben; Jones, Martin F.; Munday, Rachel; Pokar, Nisha P. B.; Screen, Thomas; Blacker, A. John [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2458 - 2473]
[6]Stirling, Matthew J.; Mwansa, Joseph M.; Sweeney, Gemma; Blacker, A. John; Page, Michael I. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 7092 - 7098]
[7]Willoughby, Christopher A.; Buchwald, Stephen L. [Journal of the American Chemical Society, 1992, vol. 114, # 19, p. 7562 - 7564]
[8]Martins, Jose E. D.; Clarkson, Guy J.; Wills, Martin [Organic Letters, 2009, vol. 11, # 4, p. 847 - 850]
[9]Li, Hao; Tian, Ping; Xu, Jian-He; Zheng, Gao-Wei [Organic Letters, 2017, vol. 19, # 12, p. 3151 - 3154]
[10]Location in patent: scheme or table Haraguchi, Naoki; Tsuru, Keiichi; Arakawa, Yukihiro; Itsuno, Shinichi [Organic and Biomolecular Chemistry, 2009, vol. 7, # 1, p. 69 - 75]
[11]Touge, Taichiro; Hakamata, Tomohiko; Nara, Hideki; Kobayashi, Tohru; Sayo, Noboru; Saito, Takao; Kayaki, Yoshihito; Ikariya, Takao [Journal of the American Chemical Society, 2011, vol. 133, # 38, p. 14960 - 14963]
[12]Blackmond, Donna G.; Ropic, Melanie; Stefinovic, Marijan [Organic Process Research and Development, 2006, vol. 10, # 3, p. 457 - 463]
[13]Leipold, Friedemann; Hussain, Shahed; Ghislieri, Diego; Turner, Nicholas J. [ChemCatChem, 2013, vol. 5, # 12, p. 3505 - 3508]
[14]Ding, Zi-Yuan; Wang, Tianli; He, Yan-Mei; Chen, Fei; Zhou, Hai-Feng; Fan, Qing-Hua; Guo, Qingxiang; Chan, Albert S. C. [Advanced Synthesis and Catalysis, 2013, vol. 355, # 18, p. 3727 - 3735]
[15]Přech, Jan; Václavík, Jiří; Šot, Petr; Pecháček, Jan; Vilhanová, Beáta; Januščák, Jakub; Syslová, Kamila; Pažout, Richard; Maixner, Jaroslav; Zápal, Jakub; Kuzma, Marek; Kačer, Petr [Catalysis Communications, 2013, vol. 36, p. 67 - 70]
[16]Velikogne, Stefan; Resch, Verena; Dertnig, Carina; Schrittwieser, Joerg H.; Kroutil, Wolfgang [ChemCatChem, 2018, vol. 10, # 15, p. 3236 - 3246]
[17]Corrêa, Bianca K.; Silva, Tamiris R.C.; Raminelli, Cristiano [Tetrahedron Letters, 2018, vol. 59, # 39, p. 3583 - 3585]

11
[ 4721-98-6 ]
[ 493-48-1 ]
[ 54193-08-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With formic acid*triethylamine In dichloromethane at 20℃; for 12h;
	With sodium tris[(S)-N-benzyloxycarbonylproline]hydroborate In dichloromethane for 22h; Ambient temperature; Yield given. Yields of byproduct given;
	With phenylsilane; hydrogen at 65℃; for 50h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

	With phthalimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; (2S,4S)-BCPM; hydrogen In toluene at 2 - 5℃; for 24h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
	With borane-THF; thiazazincolidine 1.) toluene, 0 deg C, 10 min, 2.) toluene, THF, -5 deg C, 12 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;
	With formic acid; N¹-tosyl-(1S,2S)-1,2-diamino-1,2-diphenylethane-η⁶-p-cymene complex with ruthenium chloride; triethylamine In acetonitrile at 28℃; for 3h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
	With phthalimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; (2S,4S)-BCPM; hydrogen In toluene at 2 - 5℃; for 24h; other chiral ligands and additives; var. solvents, temp., and reaction time;
	With formic acid; triethylamine; (R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine In acetonitrile for 16h; Title compound not separated from byproducts;
	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline With (-)-(1-tBu-2-TfO-1,2-azaborolyl)(cyclopentadienyl)iron In dichloromethane-d2 at 70℃; for 19h; Stage #2: With lithium triethylborohydride In tetrahydrofuran; dichloromethane at -35℃; for 2h; Stage #3: With tetrabutyl ammonium fluoride In tetrahydrofuran Title compound not separated from byproducts;
	With sodium tris<(S)-N-benzyloxycarbonylprolyloxy>hydroborate In dichloromethane for 22h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
	With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 50 - 65℃;
	With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol; <i>tert</i>-butyl alcohol at 70℃; Title compound not separated from byproducts.;
	With formic acid; triethylamine In acetonitrile at 20℃; for 0.166667h; Title compound not separated from byproducts.;
	With formic acid; triethylamine In dichloromethane at 20℃; for 0.166667h; Title compound not separated from byproducts.;
	With formic acid; triethylamine In N,N-dimethyl-formamide at 20℃; for 3h; Title compound not separated from byproducts.;
	With cetyltrimethylammonim bromide In water at 28℃; for 10h;
	With sodium formate In water at 20℃; for 24h; optical yield given as %ee;
	With formic acid; C₂₅H₂₇ClN₂O₂RuS; triethylamine In dichloromethane at 25℃; for 1.5h; optical yield given as %ee; enantioselective reaction;
	With formic acid/triethylamine complex 5:2; C₃₅H₃₅ClN₂O₂RuS In benzene-d6; acetonitrile at 28℃; for 10h; optical yield given as %ee; enantioselective reaction;
	With bis(1,5-cyclooctadiene)iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate; hydrogen; (S)-(+)-(3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']-dinaphthalen-4-yl)piperidine In toluene at 20℃; for 16h; enantioselective reaction;
	With formic acid; C₃₄H₃₂ClN₂O₂RuS; triethylamine In methanol for 6h; optical yield given as %ee; enantioselective reaction;
	With formic acid; {N-[(1R,2R)-2-((3-cyclohexa-1,4-dienyl)propyl)-(methylamino)-1,2-diphenylethyl]-4-methylbenzenesulfonamide}ruthenium chloride; triethylamine at 30℃; for 16.5h; Inert atmosphere; optical yield given as %ee;
	With formic acid; N-[(1R,2R)-2-(dimethylamino)-1,2-diphenylethyl]-4-methylbenzenesulfonamide benzene ruthenium chloride; triethylamine at 30℃; for 45h; Inert atmosphere; optical yield given as %ee;
	With formic acid; C₂₈H₃₄IrN₂⁽¹⁺⁾*F₆P^(1-); triethylamine In dichloromethane at 20℃; Inert atmosphere; enantioselective reaction;
	With formic acid; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; sodium formate In water at 28℃; for 5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	4.3. Typical procedure for the asymmetric transfer hydrogenation in water General procedure: A mixture of (R,R)-1c (3.6 mg, 0.0044 mmol) and [RhCl2(Cp∗)]2 (1.3 mg, 0.002 mmol) in a reaction tube was degassed three times. Then 1 mL of degassed water was added and the mixture stirred at 40 °C for 1 h under argon. Substrates (0.4 mmol), HCO2Na (790 mg, 11.6 mmol) and HCO2H (15.1 μL, 0.4 mmol) were then introduced. The mixture was degassed three times and stirred at 28 °C for a certain time under argon. The reaction mixture was extracted with Et2O or DCM (5 mL × 3). The conversion was determined by GC analysis and the enantioselectivity was determined by GC or HPLC analysis. The isolated yield was obtained by flash chromatography.
79 % ee	With C₄₂H₆₄Cl₄N₆O₄Rh₂S₂; streptavidin mutant K₁₂₁H; sodium formate In aq. buffer at 55℃; Schlenk technique; Inert atmosphere;
55 % ee	With C₄₂H₆₄Cl₄N₆O₄Rh₂S₂; streptavidin mutant S₁₁₂H; sodium formate In aq. buffer at 55℃; Schlenk technique; Inert atmosphere;
87 % ee	With formic acid; [RuCl(η⁶-p-cymene)(1R,2R)-N-((1S,2S)-borneol-10-sulfonyl)-1,2-diphenylethylenediamine]; triethylamine In acetonitrile at 30℃;	General procedure for asymmetric transfer hydrogenation General procedure: The formic acid-triethylamine azeotropic mixture (218 μL; 6.3 eq of formic acid with respect to the imine) was charged into a round-bottom flask (10 mL), followed by the catalyst (0.01 eq) dissolved in acetonitrile (1 mL). The resulting mixture was stirred for 10 min to activate the catalyst. The imine (0.42 mmol) dissolved in acetonitrile (1 mL) was introduced at once and the mixture was stirred at 30 °C. The samples of the reaction mixture (60 μL) were collected at 10, 20, 30, 40, 50, 90, 120 and 180 min. (0014) Each sample was quenched by using saturated solution of Na2CO3 (1 mL) and extracted with diethyl ether (3 × 1 mL). Combined extracts were dried over anhydrous sodium sulfate and the solvent was stripped off in a stream of nitrogen. The dry sample was dissolved in acetonitrile (1 mL) and analyzed.
2 % ee	With C₂₈H₂₉ClF₂IrN₃O₄S₂; sodium formate In dimethyl sulfoxide at 4℃; for 44h;
70 % ee	With C₂₈H₃₁ClIrN₃O₄S₂; sodium formate; human carbonic anhydrase II In dimethyl sulfoxide at 4℃; for 44h; Enzymatic reaction;
22 % ee	With formic acid; (R_Os,R_C)-[Os(η⁶-para-cymene)(N-(2-pyridylmethylene)-(R)-1-phenylethylamine)I]PF₆; triethylamine at 44.84℃; for 22h; Inert atmosphere;
39 % ee	With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; ATHase; C₇₁H₁₁₇N₂₁O₂₅ In aq. buffer at 37℃; Enzymatic reaction;
21 % ee	With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; ATHase; C₆₆H₉₉N₁₉O₂₃ In aq. buffer at 37℃; Enzymatic reaction;
75.6 % ee	With formic acid; N-{(1R,2R)-2-[3-(3,5-dimethoxyphenyl)propylamino]-1,2-diphenylethyl}-4-methylbenzenesulfonamide ruthenium chloride; hydrogen; triethylamine at 60℃; for 2h; Inert atmosphere;	Asymmetric transfer hydrogenation in FA:TEA: To a mixture of catalyst (0.002 mmol) in FA:TEA (5:2) (1.0 mL) was added ketone (2.0 mmol) and the mixure was stirred at 60 °C for 24h under an inert atmosphere. The reaction was monitored by TLC. After 24h, the reaction mixture was diluted with EtOAc and sat. NaHC03 soln. The organic layer was separated, washed with H20, dried over anhy. Na2S04, filtered and concentrated to give a brown residue. The crude compound was analysed by 1H-NMR to give the conversion.
41 % ee	With (2S,3R)-2-amino-3-hydroxybutanamide; streptavidin biotin-wild type; C₄₂H₆₄Cl₄Ir₂N₆O₄S₂ In dimethyl sulfoxide at 30 - 50℃; for 18h; Overall yield = 100 %; enantioselective reaction;
80 % ee	With GLUTATHIONE; PVS; streptavidin S₁₁₂A; Cp*Ir(biot-p-L)Cl; sodium formate In N,N-dimethyl-formamide at 20℃; for 48h;
63 % ee	With GLUTATHIONE; streptavidin S₁₁₂K; Cp*Ir(biot-p-L)Cl; sodium formate; α-bromoacetophenone In N,N-dimethyl-formamide at 20℃; for 48h;
89 % ee	With biotinylated Iridium complex bound S₁₁₂A strepdavidin In aq. buffer at 25℃; for 7h; Enzymatic reaction; enantioselective reaction;
78 % ee	With biotinylated Iridium complex bound S₁₁₂K strepdavidin In aq. buffer at 25℃; for 7h; Enzymatic reaction; enantioselective reaction;
	With [RuCl(TsDPEN)(hexamethylbenzene)]; formic acid; triethylamine In acetonitrile for 1.16667h; Optical yield = 82 %ee;	4.2. Standard hydrogenation procedure General procedure: The asymmetric transfer hydrogenation reactions were performed according to a previously reported procedure. A round bottom flask was equipped with a magnetic stirrer bar and was pre-heated on a water bath (30 C). Stock solutions of the substrates and catalyst were prepared. The amounts of reaction components were calculated in order to fulfill the following ratios: S/Cratio = 100, HCOOH/triethylamine ratio = 2.5, concentration = 7.0%(defined as: (mass of substrate + mass of catalyst + mass of formic acid + mass of triethylamine)/mass of solvent), hydrogenation mixture/substrate ratio = 8.83, total volume of reaction mixture = 2 mL (all ratios are molar). The components were transferred into the flask in the following order: acetonitrile, formic acid, triethylamine, solution of the catalyst. After five minutes, the calculated amount of the substrate solution containing 0.15 mmol of substrate was added into the reaction mixture. The samples were taken in defined time intervals. The samples were treated with a saturated solution of sodium carbonate (1 mL) and extracted three times with diethyl ether (3 1 mL). The extract was dried over sodium sulfate, filtered,and stripped in a stream of argon. The residue was dissolved in 600 μL of acetonitrile and analyzed via GC. After the addition of 20 μL triethylamine and 10 μL of ()-(R)-menthyl chloroformate,the enantioselectivity could be determined.
89 % ee	With formic acid; pentamethylcyclopentadienyl*RhCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]; triethylamine In methanol; water at 40℃; for 0.1h; Overall yield = 99 %; Overall yield = 202 mg; enantioselective reaction;
85 % ee	With diamide; Cp*Ir(biot-p-L)Cl; MetAlaSerMetThrGlyGlyGlnGlnMetGlyArgAspGlnAlaGlyIleThrGlyThrTrpTyrAsnGlnLeuGlySerThrPheIleValThrAlaGlyAlaAspGlyAlaLeuThrGlyThrTyrGluSerAlaValGlyAsnAlaGluSerArgTyrValLeuThrGlyArgTyrAspSerAlaProAlaThrAspGlySerGlyThrAlaLeuGlyTrpThrValAlaTrpLysAsnAsnTyrArgAsnAlaHisSerAlaThrThrTrpSerGlyGlnTyrValGlyGlyAlaGluAlaArgIleAsnThrGlnTrpLeuLeuThrLysGlyThrThrGluAlaAsnAlaTrpLysSerThrLeuValGlyHisAspThrPheThrLysValLysProSerAlaAlaSerIleAspAlaAlaLysLysAlaGlyValAsnAsnGlyAsnProLeuAspAlaValGlnGln; sodium formate In aq. buffer at 20℃; for 48h;
68 % ee	With Cp*Ir(biot-p-L)Cl; MetAlaSerMetThrGlyGlyGlnGlnMetGlyArgAspGlnAlaGlyIleThrGlyThrTrpTyrAsnGlnLeuGlySerThrPheIleValThrAlaGlyAlaAspGlyAlaLeuThrGlyThrTyrGluSerAlaValGlyAsnAlaGluSerArgTyrValLeuThrGlyArgTyrAspSerAlaProAlaThrAspGlySerGlyThrAlaLeuGlyTrpThrValAlaTrpLysAsnAsnTyrArgAsnAlaHisSerAlaThrThrTrpSerGlyGlnTyrValGlyGlyAlaGluAlaArgIleAsnThrGlnTrpLeuLeuThrLysGlyThrThrGluAlaAsnAlaTrpLysSerThrLeuValGlyHisAspThrPheThrLysValLysProSerAlaAlaSerIleAspAlaAlaLysLysAlaGlyValAsnAsnGlyAsnProLeuAspAlaValGlnGln; sodium formate In aq. buffer at 20℃; for 48h;
89 % ee	With pentamethylcyclopentadienyl*RhCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]; hydrogen; trifluoroacetic acid In methanol at 40℃; for 6h; Autoclave; Sealed tube;
80 % ee	With formic acid; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; biphenyl; triethylamine; N-[(1S,2S)-2-amino-1,2-diphenylethyl]-4-methylbenzenesulfonamide In dichloromethane at 20℃; for 0.583333h; Inert atmosphere; enantioselective reaction;
	With sodium azide In aq. acetate buffer at 40℃; for 10h; enantioselective reaction;
10 % ee	With C₄₂H₆₄Cl₄Ir₂N₆O₄S₂; SGF; streptavidin K₁₂₁A K₁₂₁A mutant In aq. buffer at 37℃; for 24h; Enzymatic reaction; enantioselective reaction;
81% ee	With C₄₂H₆₄Cl₄Ir₂N₆O₄S₂; SGF; streptavidin WT mutant In aq. buffer at 37℃; for 24h; Enzymatic reaction; enantioselective reaction;
89 % ee	With [Cp*Ir(biot-p-L)Cl] embedded on streptavifin mutant S₁₁₂A-K₁₂₁A Sav purified protein In aq. buffer at 20℃; for 48h; enantioselective reaction;
66 % ee	With [Cp*Ir(biot-p-L)Cl] embedded on streptavifin mutant S₁₁₂K Sav purified protein In aq. buffer at 20℃; for 48h; enantioselective reaction;
89 % ee	With C₃₁H₃₆ClN₂O₂RuS; hydrogen; trifluoroacetic acid In methanol for 6h; stereoselective reaction;	19 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (1) (1.22mmol) was dissolved in methanol (14.0 mL), followed by adding thereto trifluoroacetic acid (93.42 μL, 1.22mmol), and the mixture was stirred for 5 minutes. The catalyst [RuCl2 (η6-p-cymene) (S, S)-(N-tosyl-1,2-diphenylethane-1,2-diamine)] (A) (0.0122 mol) was added to the mixture (molar substrate to catalyst ratio S / C = 100).The reaction system was sealed pressure reactor and replaced three times with hydrogen (3 × 5bar), then charged with hydrogen 15bar.After 6 hours of reaction, the reaction mixture was added saturated Na2CO3Mixed solution (2mL).The resulting solution was extracted twice with ether (3 × 2mL), the combined organic phases were dried over anhydrous Na2SO4Dried for 1 hour.The resulting ether solution was evaporated to dryness in air solvent vapor, GC analysis showed 1100% of the compound is converted to 6,7-dimethyl-1-methyl-1,2,3,4-tetrahydroisoquinoline, ee value 96%.
77 % ee	With formic acid; (1,2,3,4,5-pentamethylcyclopentadienyl)Ir[κ²(N,N')-CH₃C₆H₄SO₂NCHPhCHPhNH]; phosphoric acid; triethylamine In acetonitrile enantioselective reaction;
45 % ee	With formic acid; (1,2,3,4,5-pentamethylcyclopentadienyl)Ir[κ²(N,N')-CH₃C₆H₄SO₂NCHPhCHPhNH]; phosphoric acid; triethylamine In acetonitrile for 2h; enantioselective reaction;
30 % ee	With Cp*Ir(biot-p-L)Cl; streptavidin K₁₂₁A mutant In aq. buffer at 37℃; for 48h; Sealed tube; Enzymatic reaction; enantioselective reaction;
50 % ee	With Cp*Ir(biot-p-L)Cl; streptavidin S₁₁₂T-N₁₁₈K-K₁₂₁A-S₁₂₂K mutant In aq. buffer at 37℃; for 48h; Sealed tube; Enzymatic reaction; enantioselective reaction;
71 % ee	With alcohol dehydrogenase from Lactobacillus brevis; imine reductase from Streptomyces sp. GF₃₅₈₇; NADPH In isopropyl alcohol at 30℃; for 24h; Enzymatic reaction; stereoselective reaction;
75 % ee	With sodium formate; sodium hydroxide In aq. buffer at 37℃; for 48h;
59 % ee	With recombinant FPD(K₉I-N₁₁P)-chimera streptavidin Sav-FPD, mutant S₁₁₂V-K₁₂₁A; [Cp*Ir(biot-p-L)Cl] In dimethyl sulfoxide at 25℃; for 16h; Enzymatic reaction; enantioselective reaction;
28 % ee	With sterptovidin; [Cp*Ir(biot-p-L)Cl] In dimethyl sulfoxide at 25℃; for 16h; Enzymatic reaction; enantioselective reaction;
83 % ee	With 3-(N-morpholino)propanesulfonic acid; streptavidin S₁₁₂M mutant; [η⁵η5-(biot-2-(2,3,4,5-tetramethylcyclopentadienyl)ethylamine)IrCl₂]₂; sodium formate; (R)-(-)-8-amino-5,6,7,8-tetrahydroquinoline In water at 30℃; for 18h; Enzymatic reaction;
59 % ee	With 3-(N-morpholino)propanesulfonic acid; [η⁵η5-(biot-2-(2,3,4,5-tetramethylcyclopentadienyl)ethylamine)IrCl₂]₂; sodium formate; (S)-(+)-8-amino-5,6,7,8-tetrahydroquinoline In water at 30℃; for 18h;
101.4 mg	With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C₄₂H₄₆FeP₂; hydrogen bromide; hydrogen In tetrahydrofuran; water at 30℃; for 12h; Schlenk technique; Autoclave; enantioselective reaction;
12 % ee	With Cp*Ir(biot-p-L)Cl; MASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYESAVGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTRGTTEANAWASTLVGHDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQGSGGGNGGGNGGGNGGGNIDGRGGGNASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYVTARGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTRGTTEANAWASTLVGCDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQ In dimethyl sulfoxide at 25℃; for 24h; Sealed tube;
87 % ee	With Cp*Ir(biot-p-L)Cl; MASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYESAVGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTSGTTEANAWASTLVGHDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQGSGGGNGGGNGGGNGGGNIDGRGGGNASMTGGQQMGRDQAGITGTWYAQLGDTFIVTAGADGALTGTYVTARGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTRGTTEANAWKSTLVGCDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQ In dimethyl sulfoxide at 50℃; for 48h; Sealed tube;
81 % ee	With formic acid; C₃₂H₃₁ClN₂O₃RuS; triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere; Schlenk technique; Overall yield = 71 percent; Overall yield = 74 mg; enantioselective reaction;
81 % ee	With formic acid; C₃₂H₃₁ClN₂O₃RuS; triethylamine In dichloromethane for 96h; Schlenk technique; Inert atmosphere;	General Procedure 5: Reduction of cyclic imines General procedure: To a Schlenk tube charged with the catalyst (5 mmol) was added formic acid/triethylamine 5:2 (0.25 mL) and left to stir for 15 min under a N2 atmosphere. A solution of the imine (0.5 mmol) in DCM (0.25 mL) was added to the mixture and left to stir at rt overnight. The reaction was quenched with sat. NaHC03 (5 mL) and extracted with EtOAc (3 x 5 mL). The organic layers were combined, dried over MgSO4, filtered and the solvent removed under reduced pressure. The product was purified by column chromatography gradient elution 0-60% EtOAc in Pet. Ether. Referring first to Table 1 , there is shown the results for asymmetric transfer hydrogenations using General Procedure 1 for the reduction of ketones using Catalysts 1 to 4 according to the invention.
48 % ee	With vancomycin; sodium acetate; [IrCp*((R)-2-((R)-2-(3-(N-(2-aminoethyl)sulfamoyl)benzamido)propanamido)propanoic acid)Cl]Cl In aq. buffer at 10℃; for 18h; enantioselective reaction;

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[50]Hestericová, Martina; Correro, M. Rita; Lenz, Markus; Corvini, Philippe F.-X.; Shahgaldian, Patrick; Ward, Thomas R. [Chemical Communications, 2016, vol. 52, # 60, p. 9462 - 9465]
[51]Current Patent Assignee: ZHEJIANG MENOVO PHARMACEUTICALS - CN103923005, 2016, B Location in patent: Paragraph 0046; 0049; 0050; 0051; 0052
[52]Václavíková Vilhanová, Bea; Budinská, Alena; Václavík, Jiří; Matoušek, Václav; Kuzma, Marek; Červený, Libor [European Journal of Organic Chemistry, 2017, vol. 2017, # 34, p. 5131 - 5134]
[53]Václavíková Vilhanová, Bea; Budinská, Alena; Václavík, Jiří; Matoušek, Václav; Kuzma, Marek; Červený, Libor [European Journal of Organic Chemistry, 2017, vol. 2017, # 34, p. 5131 - 5134]
[54]Hestericová, Martina; Heinisch, Tillman; Alonso-Cotchico, Lur; Maréchal, Jean-Didier; Vidossich, Pietro; Ward, Thomas R. [Angewandte Chemie - International Edition, 2018, vol. 57, # 7, p. 1863 - 1868][Angew. Chem., 2018, vol. 130, # 7, p. 1881 - 1886,6]
[55]Hestericová, Martina; Heinisch, Tillman; Alonso-Cotchico, Lur; Maréchal, Jean-Didier; Vidossich, Pietro; Ward, Thomas R. [Angewandte Chemie - International Edition, 2018, vol. 57, # 7, p. 1863 - 1868][Angew. Chem., 2018, vol. 130, # 7, p. 1881 - 1886,6]
[56]Velikogne, Stefan; Resch, Verena; Dertnig, Carina; Schrittwieser, Joerg H.; Kroutil, Wolfgang [ChemCatChem, 2018, vol. 10, # 15, p. 3236 - 3246]
[57]Hestericová, Martina; Heinisch, Tillmann; Lenz, Markus; Ward, Thomas R. [Dalton Transactions, 2018, vol. 47, # 32, p. 10837 - 10841]
[58]Zhao, Jingming; Rebelein, Johannes G.; Mallin, Hendrik; Trindler, Christian; Pellizzoni, Michela M.; Ward, Thomas R. [Journal of the American Chemical Society, 2018, vol. 140, # 41, p. 13171 - 13175]
[59]Zhao, Jingming; Rebelein, Johannes G.; Mallin, Hendrik; Trindler, Christian; Pellizzoni, Michela M.; Ward, Thomas R. [Journal of the American Chemical Society, 2018, vol. 140, # 41, p. 13171 - 13175]
[60]Facchetti, Giorgio; Rimoldi, Isabella [New Journal of Chemistry, 2018, vol. 42, # 23, p. 18773 - 18776]
[61]Facchetti, Giorgio; Rimoldi, Isabella [New Journal of Chemistry, 2018, vol. 42, # 23, p. 18773 - 18776]
[62]Nie, Huifang; Zhu, Yupu; Hu, Xiaomu; Wei, Zhao; Yao, Lin; Zhou, Gang; Wang, Pingan; Jiang, Ru; Zhang, Shengyong [Organic Letters, 2019, vol. 21, # 21, p. 8641 - 8645]
[63]Wu, Shuke; Zhou, Yi; Rebelein, Johannes G.; Kuhn, Miriam; Mallin, Hendrik; Zhao, Jingming; Igareta, Nico V.; Ward, Thomas R. [Journal of the American Chemical Society, 2019, vol. 141, # 40, p. 15869 - 15878]
[64]Wu, Shuke; Zhou, Yi; Rebelein, Johannes G.; Kuhn, Miriam; Mallin, Hendrik; Zhao, Jingming; Igareta, Nico V.; Ward, Thomas R. [Journal of the American Chemical Society, 2019, vol. 141, # 40, p. 15869 - 15878]
[65]Barrios-Rivera, Jonathan; Xu, Yingjian; Wills, Martin [Organic Letters, 2020, vol. 22, # 16, p. 6283 - 6287]
[66]Current Patent Assignee: UNIVERSITY OF WARWICK; GOLDENKEYS HIGH TECH MAT - WO2020/240178, 2020, A1 Location in patent: Page/Page column 32-33; 38
[67]Facchetti, Giorgio; Bucci, Raffaella; Fusè, Marco; Erba, Emanuela; Gandolfi, Raffaella; Pellegrino, Sara; Rimoldi, Isabella [Inorganic Chemistry, 2021, vol. 60, # 5, p. 2976 - 2982]

12
(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) [ No CAS ]
[ 4594-02-9 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
1: 81% 2: 10%	With diphenylselenium bis(trifluoroacetate) In 1,2-dimethoxyethane Ambient temperature;
	With [(η5-pentamethylcyclopentadienyl)IrCl(dipyrido[3,2-a:2',3'-c]phenazine)](CF3SO3) In aq. phosphate buffer at 37℃; for 48h; Irradiation; Inert atmosphere;

Reference： [1]Marino, J.P.; Larsen, Robert D. [Journal of the American Chemical Society, 1981, vol. 103, # 15, p. 4642 - 4643]
[2]Davis, Holly Jane; Häussinger, Daniel; Ward, Thomas R.; Okamoto, Yasunori [ChemCatChem, 2020, vol. 12, # 18, p. 4512 - 4516]

13
[ 120-20-7 ]
[ 64-19-7 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With PPA In dichloromethane at 80℃; for 3h;
73%	With polyphosphoric acid In dichloromethane at 80℃; for 3h;

Reference： [1]Venkov, Atanas P.; Ivanov, Ilian I. [Tetrahedron, 1996, vol. 52, # 37, p. 12299 - 12308]
[2]Luu, Hieu-Trinh; Wiesler, Stefan; Frey, Georg; Streuff, Jan [Organic Letters, 2015, vol. 17, # 10, p. 2478 - 2481]

14
[ 4122-57-0 ]
[ 4721-98-6 ]
C₂₈H₂₃NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.1%	at -40 - -30℃; for 0.5h;

Reference： [1]Wairener, Ronald N.; Liu, Ligong; Russell, Richard A.; Tiekink, Edward R.T. [Synlett, 1998, # 4, p. 387 - 388]

15
[ 4721-98-6 ]
[ 52401-44-2 ]
8,9-Dimethoxy-1-oxo-1,2,3,4,5,6-hexahydro-4b-azonia-chrysene; chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With diethyl amine hydrochloride In acetic acid at 100℃; for 0.5h;

Reference： [1]Mikhal'chuk; Gulyakevich; Akhrem [Russian Journal of Applied Chemistry, 1998, vol. 71, # 4, p. 667 - 669]

16
[ 4721-98-6 ]
[ 20365-21-3 ]
[ 328404-72-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In benzene for 12h; Heating;

Reference： [1]Roy, Amrita; Nandi, Sukumar; Ila, Hiriyakkanavar; Junjappa, Hiriyakkanavar [Organic Letters, 2001, vol. 3, # 2, p. 229 - 232]

17
[ 4721-98-6 ]
[ 85920-63-4 ]
9,10-dimethoxy-2-methyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 935 - 938

18
[ 4721-98-6 ]
[ 82961-73-7 ]
9,10-dimethoxy-2-phenyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride In 1,2-dichloro-ethane at 140℃; for 0.0666667h; microwave irradiation;

Reference： [1]Pemberton, Nils; Jakobsson, Lotta; Almqvist, Fredrik [Organic Letters, 2006, vol. 8, # 5, p. 935 - 938]

19
[ 4721-98-6 ]
[ 82961-73-7 ]
[ 881031-74-9 ]
9,10-dimethoxy-2-phenyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In toluene for 2h; Heating;

Reference： [1]Pemberton, Nils; Jakobsson, Lotta; Almqvist, Fredrik [Organic Letters, 2006, vol. 8, # 5, p. 935 - 938]

20
[ 4721-98-6 ]
[ 87769-40-2 ]
6,7-dihydro-9,10-dimethoxy-2-methyl-3-ethyl-benzo[a]quinolizin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With trifluoroacetic acid In 1,2-dichloro-ethane at 160℃; for 0.0333333h; microwave irradiation;

Reference： [1]Pemberton, Nils; Jakobsson, Lotta; Almqvist, Fredrik [Organic Letters, 2006, vol. 8, # 5, p. 935 - 938]

21
[ 4721-98-6 ]
[ 132415-06-6 ]
6,7-dihydro-9,10-dimethoxy-2-cyclohexyl-benzo[a]quinolizin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With trifluoroacetic acid In 1,2-dichloro-ethane at 160℃; for 0.0333333h; microwave irradiation;

Reference： [1]Pemberton, Nils; Jakobsson, Lotta; Almqvist, Fredrik [Organic Letters, 2006, vol. 8, # 5, p. 935 - 938]

22
[ 14301-36-1 ]
[ 108-24-7 ]
[ 894419-44-4 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
1: 60% 2: 13%	With PPA In dichloromethane at 50℃; for 2h;

Reference： [1]Ivanov, Iliyan; Nikolova, Stoyanka; Statkova-Abeghe, Stela; Angelov, Plamen [Heterocycles, 2006, vol. 68, # 2, p. 387 - 393]

23
[ 4721-98-6 ]
6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82 % ee	With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 75℃;	3.iv 6,7-Dimethoxy-l-methyl-l,2,3,4-tetrahydroisoquinoline, conversion >99%, ee 82% (GC, sample derivatised by treatment with acetic anhydride pyridine, Chirasil DEX CB, 25m x 0.25 mm, injector/detector 200 0C, helium 20 psi, 170 0C for 20 minutes then ramp at 5 °C/min to 200 0C, hold for 10 minutes, retention times 30.18 minutes and 30.45 minutes).
93 % ee	With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); formic acid; triethylamine In acetonitrile for 1.16667h;	4.2. Standard hydrogenation procedure General procedure: The asymmetric transfer hydrogenation reactions were performed according to a previously reported procedure. A round bottom flask was equipped with a magnetic stirrer bar and was pre-heated on a water bath (30 C). Stock solutions of the substrates and catalyst were prepared. The amounts of reaction components were calculated in order to fulfill the following ratios: S/Cratio = 100, HCOOH/triethylamine ratio = 2.5, concentration = 7.0%(defined as: (mass of substrate + mass of catalyst + mass of formic acid + mass of triethylamine)/mass of solvent), hydrogenation mixture/substrate ratio = 8.83, total volume of reaction mixture = 2 mL (all ratios are molar). The components were transferred into the flask in the following order: acetonitrile, formic acid, triethylamine, solution of the catalyst. After five minutes, the calculated amount of the substrate solution containing 0.15 mmol of substrate was added into the reaction mixture. The samples were taken in defined time intervals. The samples were treated with a saturated solution of sodium carbonate (1 mL) and extracted three times with diethyl ether (3 1 mL). The extract was dried over sodium sulfate, filtered,and stripped in a stream of argon. The residue was dissolved in 600 μL of acetonitrile and analyzed via GC. After the addition of 20 μL triethylamine and 10 μL of ()-(R)-menthyl chloroformate,the enantioselectivity could be determined.

Reference： [1]Current Patent Assignee: DOW INC; DR REDDY'S LABORATORIES LIMITED - WO2007/123957, 2007, A2 Location in patent: Page/Page column 17
[2]ot, Petr; Vilhanov, Beta; Pechek, Jan; Vclavk, Ji; Zpal, Jakub; Kuzma, Marek; Kaer, Petr [Tetrahedron Asymmetry, 2014, vol. 25, # 18-19, p. 1346 - 1351]

24
[ 4721-98-6 ]
[ 100-39-0 ]
N-benzyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In acetone	Preparation of N-Benzyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinium bromide Preparation of N-Benzyl-1-methyl-6,7-dimethoxy-3,4-dihydroisoquinolinium bromide To a stirred solution of 1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline in acetone was added benzyl bromide and the reaction mixture was stirred at room temperature for 16 hours. A yellow precipitate formed which was filtered, washed with ice cold acetone and dried in vacuo. The product was further purified by recrystallisation from a hexane/dichloromethane mix and pentane to afford the desired compound in 81% yield.
	In acetone at 20℃; for 72h;
	In ethyl acetate

Reference： [1]Current Patent Assignee: NPIL PHARMACEUTICALS UK - US6509467, 2003, B1
[2]Wu, Jiashou; Wang, Fei; Ma, Yaping; Cui, Xin; Cun, Linfeng; Zhu, Jin; Deng, Jingen; Yu, Bangliang [Chemical Communications, 2006, # 16, p. 1766 - 1768]
[3]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - WO2005/77903, 2005, A2 Location in patent: Page/Page column 28

25
[ 14301-36-1 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: 14.48 g / phosphoryl chloride / toluene / 1 h / Heating 2.1: 59.7 percent / bromophenol blue; conc. hydrochloric acid / methanol / 0 - 20 °C 3.1: KHMDS / tetrahydrofuran / 3 h / -78 °C 3.2: 177.5 mg / aq. NiCl₂ / methanol / 20 °C
	Multi-step reaction with 3 steps 1: 60 percent / polyphosphoric acid / CH₂Cl₂ / 2 h / 50 °C 2: 80 percent / pTsOH / 1,2-dichloro-ethane / 0.5 h / Heating 3: polyphophoric acid / 80 - 100 °C

Reference： [1]Werner, Frank; Blank, Nancy; Opatz, Till [European Journal of Organic Chemistry, 2007, # 23, p. 3911 - 3915]
[2]Ivanov, Iliyan; Nikolova, Stoyanka; Statkova-Abeghe, Stela; Angelov, Plamen [Heterocycles, 2006, vol. 68, # 2, p. 387 - 393]

26
[ 4721-98-6 ]
(S)-(+)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid hydrochloride salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: Pd/C / various solvent(s) / 30 h / 176 °C 2.1: aq. HBr / 27 h / 100 °C 3.1: pyridine / CH₂Cl₂ / 20 °C 4.1: (6,6'-dibromo BINOL)AlCl / CH₂Cl₂ / 48 h / -60 °C 5.1: 38 percent / hydrogen; chlorotris(triphenylphosphosphine)rhodium / ethanol; benzene / 48 h / 68404.6 Torr 6.1: thionyl chloride / ethanol / 3 h / 90 °C 6.2: aq.HCl / acetic acid / 7 h / 90 °C

Reference： [1]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]

27
[ 4721-98-6 ]
[ 1026822-75-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Pd/C / various solvent(s) / 30 h / 176 °C 2: aq. HBr / 27 h / 100 °C 3: pyridine / CH₂Cl₂ / 20 °C 4: (6,6'-dibromo BINOL)AlCl / CH₂Cl₂ / 48 h / -60 °C 5: 38 percent / hydrogen; chlorotris(triphenylphosphosphine)rhodium / ethanol; benzene / 48 h / 68404.6 Torr

Reference： [1]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]

28
[ 4721-98-6 ]
[ 123463-08-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Pd/C / various solvent(s) / 30 h / 176 °C 2: aq. HBr / 27 h / 100 °C

Reference： [1]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]

29
[ 4721-98-6 ]
[ 380427-63-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Pd/C / various solvent(s) / 30 h / 176 °C 2: aq. HBr / 27 h / 100 °C 3: pyridine / CH₂Cl₂ / 20 °C

Reference： [1]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]

30
[ 4721-98-6 ]
6,7-bis-benzoyloxy-1-cyano-1-methyl-1<i>H</i>-isoquinoline-2-carboxylic acid vinyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: Pd/C / various solvent(s) / 30 h / 176 °C 2: aq. HBr / 27 h / 100 °C 3: pyridine / CH₂Cl₂ / 20 °C 4: (6,6'-dibromo BINOL)AlCl / CH₂Cl₂ / 48 h / -60 °C

Reference： [1]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]

31
[ 4721-98-6 ]
[ 380427-49-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: Pd/C / various solvent(s) / 30 h / 176 °C 2: aq. HBr / 27 h / 100 °C 3: pyridine / CH₂Cl₂ / 20 °C 4: (6,6'-dibromo BINOL)AlCl / CH₂Cl₂ / 48 h / -60 °C

Reference： [1]Funabashi; Ratni; Kanai; Shibasaki [Journal of the American Chemical Society, 2001, vol. 123, # 43, p. 10784 - 10785]

32
[ 4721-98-6 ]
[ 98661-42-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 95 percent / sodium ethoxide / methanol / 6 h / Ambient temperature 2: 94 percent / hydrogen / platinum-on-activated-carbon catalyst / methanol
	Multi-step reaction with 2 steps 1: 45 percent / 10percent sodium hydroxide / methanol / 0.5 h / Heating 2: 94 percent / hydrogen / platinum-on-activated-carbon catalyst / methanol

Reference： [1]Kobor, Jeno; Fueloep, Ferenc; Bernath, Gabor [Heterocycles, 1986, vol. 24, # 8, p. 2227 - 2231]
[2]Kobor, Jeno; Fueloep, Ferenc; Bernath, Gabor [Heterocycles, 1986, vol. 24, # 8, p. 2227 - 2231]

33
[ 4721-98-6 ]
[ 99082-70-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium ethanolate; paraformaldehyde In methanol	1 Preparation of 1-[bis(hydroxymethyl)-methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline EXAMPLE 1 Preparation of 1-[bis(hydroxymethyl)-methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline To a suspension of 2.5 moles of paraformaldehyde in 300 ml of methanol 1 mole (205.3 g) of 1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline and subsequently freshly prepared sodium ethylate (1 g of sodium+50 ml of ethanol) are added at room temperature, with stirring. The reaction mixture is stirred for 5 to 6 hours, whereupon it is kept at 40° to 50 C.° for half an hour. The mixture is evaporated under reduced pressure and the obtained crystalline material is recrystallized from a mixture of acetone and ether. The aimed compound is obtained with a melting point of 129° to 131 C.° Yield: 90%. Analysis for C14 H19 NO4 (265.31): calculated: C 63.38%, H 7.22%, N 5.28%; found: C 63.48%, H 7.67%, N 5.17%.
70%	With sodium ethanolate; paraformaldehyde In benzene	5 Preparation of 1-[bis(hydroxymethyl)-methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline EXAMPLE 5 Preparation of 1-[bis(hydroxymethyl)-methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline To a solution of 2.5 moles of paraformaldehyde in 500 ml. of benzene 1 mole (205.3 g) of 1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline and subsequently freshly prepared sodium ethylate (1 g sodium+50 ml ethanol) are added at room temperature, with stirring. The reaction mixture is refluxed for 4 hours. The mixture is then evaporated under reduced pressure, and the obtained crystalline material is recrystallized from a mixture of acetone and ether. The aimed compound is obtained which has the same melting point as the product prepared in Example 1. Yield: 70%.
	With formaldehyd; sodium methylate In methanol	6 Preparation of 1-[bis(hydroxymethyl)-methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline EXAMPLE 6 Preparation of 1-[bis(hydroxymethyl)-methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline To 1 mole (205.3 g) of 1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline 100 ml of a 30% aqueous formaldehyde solution and then freshly prepared sodium methylate (1 g of sodium+50 ml of methanol) are added. The mixture is then slightly refluxed in 500 ml of methanol for 2 hours. The reaction mixture is evaporated under reduced pressure and the obtained crystalline product is recrystallized from a mixture of acetone and ether. The aimed compound is obtained with the same melting point as the product of Example 1.

Reference： [1]Current Patent Assignee: angolul : Chemical Works of Gedeon Richter Plc. Gedeon Richter Plc. - US4656179, 1987, A
[2]Current Patent Assignee: angolul : Chemical Works of Gedeon Richter Plc. Gedeon Richter Plc. - US4656179, 1987, A
[3]Current Patent Assignee: angolul : Chemical Works of Gedeon Richter Plc. Gedeon Richter Plc. - US4656179, 1987, A

34
[ 4721-98-6 ]
[ 60430-43-5 ]
[ 137769-96-1 ]
[ 137821-60-4 ]

Yield	Reaction Conditions	Operation in experiment
<1	With H₂; MeOH In methanol with 1 equiv. imine; not isolated, detected by NMR;

Reference： [1]Becalski, Adam G.; Cullen, William R.; Fryzuk, Michael D.; James, Brian R.; Kang, Guo-J.; Rettig, Steven J. [Inorganic Chemistry, 1991, vol. 30, # 26, p. 5002 - 5008]

35
[ 4721-98-6 ]
[ 60430-43-5 ]
[ 137821-60-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	In methanol stirring under H2 for 15 min then addn. of imine under Ar, standing at 20°C for 24 h; filtration, dried at 40°C (0.05 mmHg), elem. anal.;

Reference： [1]Becalski, Adam G.; Cullen, William R.; Fryzuk, Michael D.; James, Brian R.; Kang, Guo-J.; Rettig, Steven J. [Inorganic Chemistry, 1991, vol. 30, # 26, p. 5002 - 5008]

36
[ 4721-98-6 ]
[ 402-49-3 ]
[ 769172-81-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0 - 20℃; for 1h; Stage #2: 4-bromomethyltrifluoromethylbenzene In tetrahydrofuran; hexane at 0℃; for 1h; Stage #3: With N-((1R,2R)-2-amino-1,2-diphenylethyl)-2,4,6-trimethylbenzenesulfonamide; formic acid; triethylamine In acetonitrile for 48h;	G.3; G.3.1 3. Synthesis of 1,2,3,4-tetrahydroisoquinolines via alkylation of 1-methyl-3,4-dihydro- isoquinolines (general procedure):; At 0°C a solution of n-BuLi in hexane (1.6M, 0.63 mmol) is added drop wise to a mixture of 6,7-dimethoxy-l-methyl-3,4-dihydroisoquinoline (0.50 mmol) and diisopropylamine (0.63 mmol) in THF (1.0 mL). The reaction mixture is stirred at RT for 1h and added at 0°C to a solution of the respective benzyl bromide (0.50 mmol) in THF (1.0 mL). The solution is stirred for Ih, warmed up to RT and diluted with DCM (3.0 mL). In a second flask dichloro(p-cymene)ruthenium (II) dimer (0.15 mmol) is added to a solution of N-(( l R,2R)-2-amino- 1 ,2-diphenyl-ethyl)-2,4,6-trimethyl-benzene-sulfonamide (0.30 mmol) and triethylamine (0.60 mmol) in acetonitrile (3.3 mL). The mixture is stirred for Ih at 80°C. A portion of this solution (0.10 mL) is added to the solution of the respective dihydroisoquinoline (described above). An azeotropic mixture of formic acid and triethylamine (5: 2, 0.3 mL) is added (gas evolution). After 2d the mixture is concentrated in vacuo and purified by prep. HPLC to give the respective 1,2,3,4-tetra-hydroisoquinoline. The enantiomeric excess is determined by chiral HPLC. The absolute configuration of the respective product is assigned in analogy to the literature (N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 4916-4917).; 3.1. Synthesis of (1 S)-6,7-dimethoxy-I-[2-(4-trifluoromethyl-phenyl)-ethyl]-1,2,3,4- tetrahydroisoquinoline:; This compound is prepared by alkylation of 6,7-dimethoxy-l-methyl-3,4-dihydroiso- quinoline-with 1-bromomethyl-4-trifluoromethyl-benzene. LC-MS: rt = 0.80 min, 366 (M+1, ES+). chiral HPLC: rt = 12.0 min (hexane/ethanol 9/1; enantiomer: rt = 17.1 min).

Reference： [1]Current Patent Assignee: IDORSIA PHARMACEUTICALS LTD - WO2005/118548, 2005, A1 Location in patent: Page/Page column 23-24

37
[ 6268-86-6 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate; sodium chloride In dichloromethane Inert atmosphere;
0.74 g	With sodium hydroxide In water at 20℃; for 0.166667h;	4.2.2. 6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline (9) [17,18] To a round-bottomed flask equipped with a reflux condenser were added N-(3,4-dimethoxyphenethyl) acetamide (8) (0.89 g, 4 mmol) and toluene (4.50 mL). The mixture was heated to 40 °C under stirring and N2 atmosphere. Then, POCl3 (1.47 g, 9.6 mmol, 0.90 mL) was added dropwise using syringe and needle. The reaction was maintained under reflux for 2 h and cooled using an ice bath for 4 h. The solvent was evaporated under reduced pressure, affording an intermediate salt (m.p. 146-149 °C (m.p. Reference.18b 148-152 °C)). After that, the intermediate salt was dissolved in water (10 mL) and a 40% (w/v) aqueous solution of NaOH (10 mL) was added to the mixture, which was maintained under stirring for 10 min. The reaction was extracted with CHCl3 (3 x 20 mL). The organic phase was washed with distilled water (10 mL) and dried over MgSO4. After filtration, the solvent was evaporated under reduced pressure, affording desired product 9. Yield: 0.74 g (90%); brownish solid; m.p. 102-103 °C (m.p. Reference. 18b 105-107 °C); Rf = 0.38 (eluent: methanol); 1H NMR (300 MHz, CDCl3, ppm): δ 6.99 (s, 1H), 6.69 (s, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 3,63 (tq, J = 7.6 Hz, 1.4 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 2.37 (t, J = 1.4 Hz, 3H); 13C NMR (75 MHz, CDCl3, ppm): δ 163.6, 150.8, 147.4, 131.0, 122.4, 110.1,108.9, 56.1, 55.9, 46.9, 25.7, 23.3; IR (KBr, cm-1) 2993.5, 2962.6, 2922.1, 1602.8, 1514.1, 1408.4, 1350.1, 1213.2, 1060.8; GC/MS (m/z, %): 205 (100.0), 190 (57.9), 174 (21.5), 160 (21.4), 147 (12.8), 132 (4.3). Characterization data are in accordance with the literature[17b,32].

Reference： [1]Soni, Rina; Cheung, Fung Kei; Clarkson, Guy C.; Martins, Jose E. D.; Graham, Mark A.; Wills, Martin [Organic and Biomolecular Chemistry, 2011, vol. 9, # 9, p. 3290 - 3294]
[2]Casagrande, Gleison A.; Deflon, Victor M.; Martins, Gabriel R.; Oliveira-Silva, Diogo; Perecim, Givago P.; Pinto, Leandro M. C.; Raminelli, Cristiano [Tetrahedron, 2020]

38
[ 4721-98-6 ]
[ 333-27-7 ]
CF₃O₃S^(1-)*C₁₃H₁₈NO₂⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃; for 1.16667h; Inert atmosphere;	4.2. Typical procedure for the reaction of cyclic imines 1 with TMSCF₂SO₂Ph (2) General procedure: Under a nitrogen atmosphere, into a CH2Cl2 (8 mL) solution of cyclic imine 1a (96 mg, 0.5 mmol) was added MeOTf (0.068 mL, 0.6 mmol) dropwise in 10 min. After the reaction mixture was stirred for 1 h at ambient temperature, the solvent CH2Cl2 was gently evaporated and dry DMF (3 mL) and KF (87 mg, 1.5 mmol) were added. Then a DMF (2 mL) solution of TMSCF2SO2Ph (2) (264 mg, 1.0 mmol) was added to the reaction system dropwise in 10 min. After stirring at ambient temperature for 30 min, the reaction mixture was quenched with a saturated NaHCO3 aqueous solution (20 mL) and extracted with ethyl acetate (3×15 mL). The combined organic phase was washed with saturated NaHCO3 solution (15 mL), and dried by anhydrous Na2SO4. After the removal of the solvent under reduced pressure, the residue was purified by flash column chromatography (petroleum ether/ethyl acetate, 3:1) to give 3a as a pale yellow solid (187 mg, 94%).

Reference： [1]Location in patent: experimental part Huang, Weizhou; Ni, Chuanfa; Zhao, Yanchuan; Zhang, Wei; Dilman, Alexander D.; Hu, Jinbo [Tetrahedron, 2012, vol. 68, # 26, p. 5137 - 5144]

39
[ 4721-98-6 ]
[ 70-23-5 ]
[ 20353-71-3 ]

Yield	Reaction Conditions	Operation in experiment
2.1 g	With potassium carbonate In ethanol for 3h; Reflux;	5.a (a), ethyl 8,9-dimethoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-2-carboxylate (a), ethyl 8,9-dimethoxy-5,6-dihvdropyrrolo[2,1 -alisoquinoline-2-carboxylate To a mixture of 1 -methyl-6,7-dimethoxy-3,4-dihydroisoquinoline (2 g) and potassium carbonate (2.4 g) in ethanol (50 ml) was added dropwise ethylbromopyruvate (1.22 ml). The reaction mixture was refluxed for 3 hrs. The reaction was allowed to cool to ambient temperature before a saturated aqueous NaHC03 solution was added. The aqueous phase was extracted with ethyl acetate twice. The combined organic layers were washed with brine. The organic layer was dried (MgS04), filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with heptane and increasing amounts of ethyl acetate. Yield: 2.1 g MS (ESI) m/z: 302 (M+H)+.

Reference： [1]Current Patent Assignee: CHARLES RIVER LABORATORIES INTERNATIONAL INC - WO2013/41458, 2013, A1 Location in patent: Page/Page column 35; 36

40
[ 4721-98-6 ]
[ 75-26-3 ]
6,7-diisopropoxy-1-methyl-3,4-dihydroisoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline With hydrogen bromide In water at 90℃; Stage #2: isopropyl bromide With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 21h;	30.a (a). 6,7-diisopropoxy-1-methyl-3,4-dihydroisoquinoline (a). 6,7-diisopropoxy-1 -methyl-3,4-dihvdroisoquinoline A solution of 1 -methyl-6,7-dimethoxy-3,4-dihydroisoquinoline (35.8 g) in aqueous HBr (48 %, 175 ml) was heated at 90°C for 4,5 hours. 1 1 % starting material, 71 % mono-demethyl and 18% di-demethyl product according to LC-MS. Toluene was added to the reaction mixture and the solvent was evaporated in vacuo. The residue was dissolved in DMF (300 ml), before addition of potassium carbonate (82 g). 2-Bromopropane (41 ,7 ml) was added to the stirred suspension before heating at 70°C for 18 hrs. 40% conversion according to LC-MS, hence a further aliquot of 2-bromopropane and potassium carbonate were added to the reaction mixture and heated at 70°C for 3 hrs. The reaction mixture was extracted with ethyl acetate and water. The aqueous layer was washed with ethyl acetate and the combined organic layers were washed sequentially with water and brine, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel with petrol and increasing amounts of ethyl acetate, yielding in a pale brown solid 0.7 g, consisting of 82% mono-demethyl product, 8% di-demethyl product and 12% starting material. This material was used without further purification.

Reference： [1]Current Patent Assignee: CHARLES RIVER LABORATORIES INTERNATIONAL INC - WO2013/41458, 2013, A1 Location in patent: Page/Page column 52; 53

41
[ 4721-98-6 ]
[ 54193-08-7 ]

Yield	Reaction Conditions	Operation in experiment
98.5%	With Cp*Ir(biot-p-L)Cl; MASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYESAVGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTSGTTEANAWASTLVGHDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQGSGGGNGGGNGGGNGGGNIDGRGGGNASMTGGQQMGRDQAGITGTWYAQLGDTFIVTAGADGALTGTYVTARGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTRGTTEANAWKSTLVGCDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQ In dimethyl sulfoxide at 25℃; for 48h; Sealed tube;
97%	With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; (1S,2S)-N-toluenesulfonyl-1,2-diphenylethylenediamine; sodium formate In methanol; water at 40℃; for 0.333333h; enantioselective reaction;
94%	With (1S,2S)-(+)-N-tosyl-1,2-diphenylethane-1,2-diamine[η6-1-isopropyl-4-methylbenzene]-ruthenium(II); formic acid; triethylamine In acetonitrile at 30℃; Inert atmosphere;

87%	With Noyori's catalyst; formic acid; triethylamine In acetonitrile at 28℃; for 2h;
93 % ee	With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); formic acid; triethylamine In [D₃]acetonitrile
93 % ee	With biotinylated Iridium complex bound S₁₁₂A strepdavidin In aq. buffer at 25℃; for 7h; Enzymatic reaction;
90 % ee	With Cp*Ir(biot-p-L)Cl; MetAlaSerMetThrGlyGlyGlnGlnMetGlyArgAspGlnAlaGlyIleThrGlyThrTrpTyrAsnGlnLeuGlySerThrPheIleValThrAlaGlyAlaAspGlyAlaLeuThrGlyThrTyrGluSerAlaValGlyAsnAlaGluSerArgTyrValLeuThrGlyArgTyrAspSerAlaProAlaThrAspGlySerGlyThrAlaLeuGlyTrpThrValAlaTrpLysAsnAsnTyrArgAsnAlaHisSerAlaThrThrTrpSerGlyGlnTyrValGlyGlyAlaGluAlaArgIleAsnThrGlnTrpLeuLeuThrAlaGlyThrThrGluAlaAsnAlaTrpLysSerThrLeuValGlyHisAspThrPheThrLysValLysProSerAlaAlaSerIleAspAlaAlaLysLysAlaGlyValAsnAsnGlyAsnProLeuAspAlaValGlnGln; sodium formate In aq. buffer at 20℃; for 4.5h;
96 % ee	With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); hydrogen; trifluoroacetic acid In methanol at 40℃; for 6h; Autoclave; Sealed tube;
	Multi-step reaction with 2 steps 1: potassium borohydride / methanol / 5.33 h / 20 °C 2: (S)-Mandelic acid / ethanol / 3 h / Reflux
90 % ee	With [Cp*Ir(biot-p-L)Cl] embedded on streptavifin mutant S₁₁₂A immobilized on protected silica nanoparticles In aq. buffer at 20℃; for 48h; enantioselective reaction;
96 % ee	With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); hydrogen; trifluoroacetic acid In methanol for 6h; stereoselective reaction;	1 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (1) (1.22mmol) was dissolved in methanol (14.0 mL), followed by adding thereto trifluoroacetic acid (93.42 μL, 1.22mmol), and the mixture was stirred for 5 minutes. The catalyst [RuCl2 (η 6-p-cymene) (S, S)-(N-tosyl-1,2-diphenylethane-1,2-diamine)] (A) (0.0122 mol) was added to the mixture (molar substrate to catalyst ratio S / C = 100).The reaction system was sealed pressure reactor and replaced three times with hydrogen (3 × 5bar), then charged with hydrogen 15bar.After 6 hours of reaction, the reaction mixture was added saturated Na2CO3Mixed solution (2mL).The resulting solution was extracted twice with ether (3 × 2mL), the combined organic phases were dried over anhydrous Na2SO4 dried for 1 hour. The resulting ether solution was evaporated to dryness in air solvent vapor, GC analysis showed 1100% of the compound is converted to 6,7-dimethyl-1-methyl-1,2,3,4-tetrahydroisoquinoline, ee value 96%.
	Multi-step reaction with 3 steps 1: sodium tetrahydroborate / water; isopropyl alcohol / 5 h / 0 - 20 °C 2: μ-diiodo-di((η5-pentamethylcyclopentadienyl)(iodo)iridium); sodium chloride / toluene; water / 48 h / 40 - 50 °C / Enzymatic reaction 3: lithium hydroxide monohydrate; water / ethanol / 1 h / 180 °C / Microwave irradiation

Reference： [1]Wu, Shuke; Zhou, Yi; Rebelein, Johannes G.; Kuhn, Miriam; Mallin, Hendrik; Zhao, Jingming; Igareta, Nico V.; Ward, Thomas R. [Journal of the American Chemical Society, 2019, vol. 141, # 40, p. 15869 - 15878]
[2]Shende, Vaishali S.; Shingote, Savita K.; Deshpande, Sudhindra H.; Kuriakose, Nishamol; Vanka, Kumar; Kelkar, Ashutosh A. [RSC Advances, 2014, vol. 4, # 86, p. 46351 - 46356]
[3]Kwan, Maria H. T.; Breen, Jessica; Bowden, Martin; Conway, Louis; Crossley, Ben; Jones, Martin F.; Munday, Rachel; Pokar, Nisha P. B.; Screen, Thomas; Blacker, A. John [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2458 - 2473]
[4]Stirling, Matthew J.; Mwansa, Joseph M.; Sweeney, Gemma; Blacker, A. John; Page, Michael I. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 7092 - 7098]
[5]Vaclavik, Jiri; Pechacek, Jan; Vilhanova, Beata; Sot, Petr; Januscak, Jakub; Matousek, Vaclav; Prech, Jan; Bartova, Simona; Kuzma, Marek; Kacer, Petr [Catalysis Letters, 2013, vol. 143, # 6, p. 555 - 562]
[6]Robles, Victor Muoz; Dürrenberger, Marc; Heinisch, Tillmann; Lleds, Agust; Schirmer, Tilman; Ward, Thomas R.; Marchal, Jean-Didier [Journal of the American Chemical Society, 2014, vol. 136, # 44, p. 15676 - 15683]
[7]Current Patent Assignee: UNIVERSITY OF BASEL - EP2952497, 2015, A1 Location in patent: Page/Page column 7; 8; 9
[8]Vilhanová; Václavík; Šot; Pecháček; Zápal; Pažout; Maixner; Kuzma; Kačer [Chemical Communications, 2016, vol. 52, # 2, p. 362 - 365]
[9]Zhu, Ruiheng; Xu, Zhangli; Ding, Wei; Liu, Shiling; Shi, Xiaoxin; Lu, Xia [Chinese Journal of Chemistry, 2014, vol. 32, # 10, p. 1039 - 1048]
[10]Hestericová, Martina; Correro, M. Rita; Lenz, Markus; Corvini, Philippe F.-X.; Shahgaldian, Patrick; Ward, Thomas R. [Chemical Communications, 2016, vol. 52, # 60, p. 9462 - 9465]
[11]Current Patent Assignee: ZHEJIANG MENOVO PHARMACEUTICALS - CN103923005, 2016, B Location in patent: Paragraph 0045; 0046
[12]Corrêa, Bianca K.; Silva, Tamiris R.C.; Raminelli, Cristiano [Tetrahedron Letters, 2018, vol. 59, # 39, p. 3583 - 3585]

42
[ 4721-98-6 ]
[ 5394-63-8 ]
9,10-dimethoxy-2-methyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42 mg	In toluene at 150℃; for 0.0833333h; Irradiation; Inert atmosphere;	4.1.2.1 9,10-Dimethoxy-2-methyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one (1b) 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.065mL, 0.48mmol) was added to a stirred solution of imine 1a (50mg, 0.24mmol) dissolved in dry toluene (0.5mL). The mixture was irradiated at 150°C, 300W, for 5minand then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-MeOH, 98:2) gave 1b (42mg, 70%) as a white powder. Characterization data were in agreement with published data [33,31].

Reference： [1]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]

43
[ 4721-98-6 ]
[ 5394-63-8 ]
[ 1491132-39-8 ]

Yield	Reaction Conditions	Operation in experiment
43 mg	With triethylamine In toluene for 3h; Reflux; Inert atmosphere;	4.1.3.1 9,10-Dimethoxy-2,11b-dimethyl-7,11b-dihydro-4H,6H- [1,3]oxazino[2,3-a]isoquinolin-4-one (1c) 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.06mL, 0.44mmol) was added to a stirred solution of imine 1a (46mg, 0.22mmol) dissolved in dry toluene (5mL). Et3N (0.06mL, 0.44mmol) was added and the heated mixture was refluxed for 3h and then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-AcOEt, 60:40) gave 1c (43mg, 68%). IR (cm-1): 2932, 1662, 1515, 1409; 1H NMR (500MHz, CDCl3): δ=6.99 (s, 1H, H-8), 6.96 (s, 1H, H-11), 5.26 (s, 1H, H-3), 4.62 (ddd, J=12.7, 5.1, 2.7Hz; 1H, H-6α), 3.91 (s, 3H, OCH3-9), 3.66 (s, 3H, OCH3-10), 3.01 (m, 1H, H-6β), 2.91 (m, 1H, H-7α), 2.66 (m, 1H, H-7β), 1.97 (CH3-2), 1.81 (CH3-11b); 13C NMR (125MHz, CDCl3): δ=163.4 (CO), 162.1 (C-2), 149.2 (C-10), 148.8 (C-9), 128.5 (C-11a), 126.9 (C-7a), 110.7 (CH-8), 108.8 (CH-11), 98.4 (CH-3), 90.3 (C-11b), 56.1 (OCH3-10), 55.8 (OCH3-9), 35.9 (CH2-6), 27.6 (CH2-7), 23.1 (CH3-11b), 19.8 (CH3-2); ESMS m/z (%) 290 [M+H]+ (100)

Reference： [1]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]

44
[ 4721-98-6 ]
[ 77092-12-7 ]
9,10-dimethoxy-2-phenyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35 mg	In toluene at 110℃; for 0.0833333h; Irradiation; Inert atmosphere;	4.1.2.1 9,10-Dimethoxy-2-methyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one (1b) General procedure: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.065mL, 0.48mmol) was added to a stirred solution of imine 1a (50mg, 0.24mmol) dissolved in dry toluene (0.5mL). The mixture was irradiated at 150°C, 300W, for 5minand then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-MeOH, 98:2) gave 1b (42mg, 70%) as a white powder. Characterization data were in agreement with published data [33,31].

Reference： [1]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]

45
[ 4721-98-6 ]
[ 77092-12-7 ]
[ 881031-74-9 ]

Yield	Reaction Conditions	Operation in experiment
40 mg	With triethylamine In toluene for 3h; Reflux; Inert atmosphere;	4.1.3.1 9,10-Dimethoxy-2,11b-dimethyl-7,11b-dihydro-4H,6H- [1,3]oxazino[2,3-a]isoquinolin-4-one (1c) General procedure: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.06mL, 0.44mmol) was added to a stirred solution of imine 1a (46mg, 0.22mmol) dissolved in dry toluene (5mL). Et3N (0.06mL, 0.44mmol) was added and the heated mixture was refluxed for 3h and then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-AcOEt, 60:40) gave 1c (43mg, 68%).

Reference： [1]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]

46
[ 4721-98-6 ]
[ 1293991-93-1 ]
[ 1491132-40-1 ]

Yield	Reaction Conditions	Operation in experiment
23 mg	In toluene at 110℃; for 0.0833333h; Irradiation; Inert atmosphere;	4.1.2.1 9,10-Dimethoxy-2-methyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one (1b) General procedure: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.065mL, 0.48mmol) was added to a stirred solution of imine 1a (50mg, 0.24mmol) dissolved in dry toluene (0.5mL). The mixture was irradiated at 150°C, 300W, for 5minand then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-MeOH, 98:2) gave 1b (42mg, 70%) as a white powder. Characterization data were in agreement with published data [33,31].

Reference： [1]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]

47
[ 4721-98-6 ]
[ 1293991-93-1 ]
[ 1491132-41-2 ]

Yield	Reaction Conditions	Operation in experiment
20 mg	With triethylamine In toluene for 3h; Reflux; Inert atmosphere;	4.1.3.1 9,10-Dimethoxy-2,11b-dimethyl-7,11b-dihydro-4H,6H- [1,3]oxazino[2,3-a]isoquinolin-4-one (1c) General procedure: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.06mL, 0.44mmol) was added to a stirred solution of imine 1a (46mg, 0.22mmol) dissolved in dry toluene (5mL). Et3N (0.06mL, 0.44mmol) was added and the heated mixture was refluxed for 3h and then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-AcOEt, 60:40) gave 1c (43mg, 68%).

Reference： [1]Moreno, Laura; Cabedo, Nuria; Boulangé, Agathe; Párraga, Javier; Galán, Abraham; Leleu, Stéphane; Sanz, María-Jesús; Cortes, Diego; Franck, Xavier [European Journal of Medicinal Chemistry, 2013, vol. 69, p. 69 - 76]

48
[ 4721-98-6 ]
C₁₃H₉NO₂ [ No CAS ]
[ 1606990-78-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With zinc(II) chloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Eschenbrenner-Lux, Vincent; Kuechler, Philipp; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert [Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2134 - 2137][Angew. Chem., 2014, vol. 126, # 8, p. 2166 - 2169,4]

49
[ 4721-98-6 ]
[ 55593-91-4 ]
[ 1606990-85-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	With zinc(II) chloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Eschenbrenner-Lux, Vincent; Kuechler, Philipp; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert [Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2134 - 2137][Angew. Chem., 2014, vol. 126, # 8, p. 2166 - 2169,4]

50
[ 4721-98-6 ]
C₁₂H₅Cl₂NO₂ [ No CAS ]
[ 1606990-81-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With zinc(II) chloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Eschenbrenner-Lux, Vincent; Kuechler, Philipp; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert [Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2134 - 2137][Angew. Chem., 2014, vol. 126, # 8, p. 2166 - 2169,4]

51
[ 4721-98-6 ]
C₁₄H₁₂O₄ [ No CAS ]
[ 1606990-77-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	With zinc(II) chloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Eschenbrenner-Lux, Vincent; Kuechler, Philipp; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert [Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2134 - 2137][Angew. Chem., 2014, vol. 126, # 8, p. 2166 - 2169,4]

52
[ 4721-98-6 ]
[ 55593-92-5 ]
[ 1606990-84-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With zinc(II) chloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Eschenbrenner-Lux, Vincent; Kuechler, Philipp; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert [Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2134 - 2137][Angew. Chem., 2014, vol. 126, # 8, p. 2166 - 2169,4]

53
[ 4721-98-6 ]
C₁₃H₈Cl₂O₄ [ No CAS ]
[ 1606990-80-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With zinc(II) chloride In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Eschenbrenner-Lux, Vincent; Kuechler, Philipp; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert [Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2134 - 2137][Angew. Chem., 2014, vol. 126, # 8, p. 2166 - 2169,4]

54
[ 4721-98-6 ]
[ 140-29-4 ]
1-(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)-2-phenylethan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; phenylacetonitrile With manganese; chloro-trimethyl-silane; bis(cyclopentadienyl)titanium(IV) diphenoxide; triethylamine hydrochloride In tetrahydrofuran at 60℃; for 24h; Schlenk technique; Inert atmosphere; Stage #2: With hydrogenchloride; water In tetrahydrofuran; diethyl ether; dichloromethane Cooling; regioselective reaction;

Reference： [1]Luu, Hieu-Trinh; Wiesler, Stefan; Frey, Georg; Streuff, Jan [Organic Letters, 2015, vol. 17, # 10, p. 2478 - 2481]

55
[ 4721-98-6 ]
[ 3088-44-6 ]
3-(allyloxy)-1-(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; 3-allyloxy-propionitrile With chloro-trimethyl-silane; bis(cyclopentadienyl)titanium(IV) diphenoxide; triethylamine hydrochloride; zinc In tetrahydrofuran at 60℃; for 16h; Schlenk technique; Inert atmosphere; Stage #2: With hydrogenchloride; water In tetrahydrofuran; diethyl ether; dichloromethane Cooling; regioselective reaction;

Reference： [1]Luu, Hieu-Trinh; Wiesler, Stefan; Frey, Georg; Streuff, Jan [Organic Letters, 2015, vol. 17, # 10, p. 2478 - 2481]

56
[ 4721-98-6 ]
[ 42202-44-8 ]
3-(allyloxy)-1-(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; 3-trimethylsilanyloxypropionitrile With chloro-trimethyl-silane; bis(cyclopentadienyl)titanium(IV) diphenoxide; triethylamine hydrochloride; zinc In tetrahydrofuran at 60℃; for 16h; Schlenk technique; Inert atmosphere; Stage #2: With hydrogenchloride; water In tetrahydrofuran; diethyl ether; dichloromethane Cooling; regioselective reaction;

Reference： [1]Luu, Hieu-Trinh; Wiesler, Stefan; Frey, Georg; Streuff, Jan [Organic Letters, 2015, vol. 17, # 10, p. 2478 - 2481]

57
[ 4721-98-6 ]
[ 883-87-4 ]
[ 110691-65-1 ]

Yield	Reaction Conditions	Operation in experiment
79 % ee	With glucose dehydrogenase; D-Glucose; Amycolatopsis orientalis (Uniprot R₄SNK₄) imine reductase; NADP In aq. phosphate buffer; N,N-dimethyl-formamide at 30℃; for 18h; Enzymatic reaction; stereoselective reaction;

Reference： [1]Aleku, Godwin A.; Man, Henry; France, Scott P.; Leipold, Friedemann; Hussain, Shahed; Toca-Gonzalez, Laura; Marchington, Rebecca; Hart, Sam; Turkenburg, Johan P.; Grogan, Gideon; Turner, Nicholas J. [ACS Catalysis, 2016, vol. 6, # 6, p. 3880 - 3889]

58
[ 4721-98-6 ]
(S)-6,7-dimethoxy-1-deutero-1-methyl-1,2,3,4-tetrahydroisoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With [Ru(η6-p-cymene)(HNC(Ph)C(Ph)NTs)]; deuterated formic acid; triethylamine In acetonitrile at 28℃; for 2h;

Reference： [1]Stirling, Matthew J.; Mwansa, Joseph M.; Sweeney, Gemma; Blacker, A. John; Page, Michael I. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 7092 - 7098]

59
[ 4721-98-6 ]
(R)-6,7-dimethoxy-1-deutero-1-methyl-1,2,3,4-tetrahydroisoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With Noyori's catalyst; deuterated formic acid; triethylamine In acetonitrile at 28℃; for 2h;

Reference： [1]Stirling, Matthew J.; Mwansa, Joseph M.; Sweeney, Gemma; Blacker, A. John; Page, Michael I. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 7092 - 7098]

60
(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) [ No CAS ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With cerium(III) chloride; 2-iodoxybenzoic acid In acetonitrile at 20℃; for 4h; Inert atmosphere;

Reference： [1]Hati, Santanu; Sen, Subhabrata [European Journal of Organic Chemistry, 2017, vol. 2017, # 9, p. 1277 - 1280]

61
[ 4721-98-6 ]
[ 80-48-8 ]
6,7-dimethoxy-1,2-dimethyl-3,4-dihydroisoquinolinium toluene-4-sulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In toluene at 60℃; for 4h; Inert atmosphere;	3 Synthesis of 6,7-dimethoxy- 1 ,2-dimethy 1-3,4- dihydroisoquinolinium toluene-4-sulfonate (compound 3) 20 g of l-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline (1 eq.) and 18.5 g (1.02 eq.) of para-toluenesulfonyl methyl ester are placed in 70 ml of toluene in a 100 ml three-necked flask. The mixture is heated under argon at a temperature of 60°C for 4 hours. A brown precipitate is filtered off and washed with acetone. 3.4 g (98% yield) of compound (3) are obtained in the form of a yellow powder. (0227) The NMR and mass analyses are in accordance with the expected structure

Reference： [1]Current Patent Assignee: L'OREAL SA - WO2017/109185, 2017, A1 Location in patent: Page/Page column 28

62
[ 4721-98-6 ]
6,7-dimethoxy-1-(methyl-d3)-3,4-dihydroisoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With water-d2; sodium carbonate at 80℃; for 18h;
96%	With water-d2; sodium carbonate at 80℃; for 18h;

Reference： [1]Chithanna, Sivanna; Yang, Ding-Yah [New Journal of Chemistry, 2021, vol. 45, # 14, p. 6495 - 6502]
[2]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

63
[ 4721-98-6 ]
[ 91-64-5 ]
(10RS,15aRS)-2,3-dimethoxy-9,10-dihydro-5H-10,15a methanobenzo[7,8][1,3]oxazocino[2,3-a]isoquinolin-8(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium carbonate In water at 80℃; for 16h; stereoselective reaction;

Reference： [1]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

64
[ 93-35-6 ]
[ 4721-98-6 ]
(10RS,15aRS)-13-hydroxy-2,3-dimethoxy-9,10-dihydro-5H-10,15a-methanobenzo[7,8][1,3]-oxazocino[2,3-a]isoquinolin-8(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium carbonate In water at 80℃; for 18h; stereoselective reaction;

Reference： [1]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

65
[ 531-59-9 ]
[ 4721-98-6 ]
(10RS,15aRS)-2,3,13-trimethoxy-9,10-dihydro-5H-10,15a-methanobenzo[7,8][1,3]oxazocino-[2,3-a]isoquinolin-8(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium carbonate In water at 80℃; for 16h; stereoselective reaction;

Reference： [1]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

66
[ 92-61-5 ]
[ 4721-98-6 ]
(10RS,15aRS)-13-hydroxy-2,3,12-trimethoxy-9,10-dihydro-5H-10,15a-methanobenzo[7,8][1,3]-oxazocino[2,3-a]isoquinolin-8(6H)-one [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 4015 - 4019

67
[ 66-97-7 ]
[ 4721-98-6 ]
(10RS,16aRS)-2,3-dimethoxy-9,10-dihydro-5H-10,16a-methanobenzofuro[5',6':7,8][1,3]oxazocino[2,3-a]isoquinolin-8(6H)-one [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 4015 - 4019

68
[ 955-10-2 ]
[ 4721-98-6 ]
(10RS,15aRS)-2,3-dimethoxy-9-phenyl-9,10-dihydro-5H-10,15a-methanobenzo[7,8][1,3]oxazocino[2,3-a]isoquinolin-8(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With sodium carbonate In water at 80℃; for 18h; stereoselective reaction;

Reference： [1]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

69
[ 4721-98-6 ]
[ 2549-08-8 ]
N-((10SR,15aRS)-2,3-dimethoxy-8-oxo-6,8,9,10-tetrahydro-5H-10,15a-methanobenzo-[7,8][1,3]oxazocino[2,3-a]isoquinolin-9-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With sodium carbonate In water at 80℃; for 18h; stereoselective reaction;

Reference： [1]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

70
[ 15795-54-7 ]
[ 4721-98-6 ]
9,10-dimethoxy-2-(4-methoxyphenyl)-6,7-dihydro-2H-pyrido[2,1-a]isoquinolin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With sodium carbonate In water at 80℃; for 16h;

Reference： [1]Pramthaisong, Chiranan; Worayuthakarn, Rattana; Pharikronburee, Vannapha; Duangthongyou, Tanwawan; Rattanakam, Ramida; Ruchirawat, Somsak; Thasana, Nopporn [Organic Letters, 2018, vol. 20, # 13, p. 4015 - 4019]

71
[ 4721-98-6 ]
[ 4522-93-4 ]
C₁₉H₁₄F₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline With n-butyllithium; lithium diisopropyl amide In tetrahydrofuran at -70℃; for 1h; Stage #2: ethyl pentafluorobenzoate at 20℃;

Reference： [1]Sóvári, Dénes; Kormos, Attila; Demeter, Orsolya; Dancsó, András; Keser, György Miklós; Milen, Mátyás; Ábrányi-Balogh, Péter [RSC Advances, 2018, vol. 8, # 67, p. 38598 - 38605]

72
[ 4721-98-6 ]
[ 100-39-0 ]
2-benzyl-6,7-dimethoxy-1-phenethyl-3,4-dihydroisoquinolin-2-ium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 2h; chemoselective reaction;	General Procedure for the Preparation of 3. General procedure: To a solutionof DHIQ 1a (100 mg, 0.571 mmol, 1.0 equiv) in CH3CN (1.0 mL) was added alkyl or benzyl halides (2.85 mmol, 5.0 equiv) followed by DIPEA (0.11 mL,0.628 mmol, 1.1 equiv) at rt. The reaction mixture was stirred at rt. for 2 to 5 h and then the solvent was evaporated under reduced pressure. The crude mixture was quenched with 0.5 M HCl (aq) and extracted with DCM (3 X25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gel column chromatography using DCM/MeOH (9/1) as an eluent toafford 3.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

73
[ 4721-98-6 ]
[ 74-88-4 ]
6,7-dimethoxy-2-methyl-1-(3,4-methylenedioxyphenethyl)-3,4-dihydroquinolinium iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 2h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 4h; chemoselective reaction;	6,7-Dimethoxy-2-methyl-1-phenethyl-3,4-dihydroisoquinolin-2-ium chloride (4i): A solution of 1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg, 0.268 mmol),5-(bromomethyl)-1.3-benzodioxole (77.4 mg, 0.366 mmol),and DIPEA (34.9 mg, 0.268 mmol) in CH3CN (1.0 mL)was stirred at rt. When 1d was completely consumed in 2 h based on the analysis of TLC and LC/MS, NaI (5.5 mg,0.0367 mmol) was added to the reaction mixture and stirredat rt. for 4 h. The crude mixture was quenched with 0.5 NHCl (aq) and extracted with DCM (2 × 25 mL). The combinedorganic layers were dried over anhydrous Na2SO4and the solvent was removed under vacuum. The crudemixture was purified on silica gel column chromatographyusing DCM/MeOH (9/1) as an eluent to afford 4 h (70 mg,0.15 mmol, 60%) as a slightly yellow solid. 1H NMR(300 MHz, CDCl3) δ 7.11 (s, 1H), 6.88 (s, 1H), 6.67 (d,J = 7.8 Hz, 1H), 6.58 (d, J = 1.6 Hz, 1H), 6.53 (d,J = 7.8 Hz, 1H), 5.91 (s, 2H), 4.06 (t, J = 7.7 Hz, 2H),3.99 (s, 3H), 3.87 (s, 3H), 3.72 (s, 3H), 3.56 (t,J = 7.2 Hz, 2H), 3.20 (t, J = 7.8 Hz, 2H), 3.00 (t, J = 7.1Hz,2H); 13C NMR (125 MHz, CDCl3) δ 176.5, 156.4, 148.8,148.1, 147.0, 133.2, 131.5, 121.5, 118.9, 112.3, 110.8,108.7, 101.3, 56.8, 56.7, 53.5, 46.2, 34.4, 33.7, 26.1;LC/MS m/z 354.1 [M + H+]; EDS (atoms present): C,H, O, N, I.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

74
[ 4721-98-6 ]
[ 100-44-7 ]
[ 74-88-4 ]
6,7-dimethoxy-2-methyl-1-phenethyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; benzyl chloride; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 2h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 4h; chemoselective reaction;	6,7-Dimethoxy-2-methyl-1-phenethyl-3,4-dihydroisoquinolin-2-ium chloride (4a): A solution of 1d (50.0 mg,0.244 mmol), methyl iodide (37.3 mg, 0.268 mmol), benzylchloride (46.2 mg, 0.366 mmol), and DIPEA (34.9 mg,0.268 mmol) in CH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 2 h based on the analysis of TLC and LC/MS, NaI (5.5 mg, 0. 037 mmol) was addedto the reaction mixture and stirred at rt. for 4 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracte dwith DCM (2 × 25 mL). The combined organic layers weredried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gelcolumn chromatography using DCM/MeOH (9/1) as aneluent to afford 4a (90 mg, 0.21 mmol, 84%) as a yellowoil. 1H NMR (300 MHz, CDCl3) δ 7.28-7.24 (m, 3H),7.12-7.09 (m, 3H), 6.88 (s, 1H), 4.04 (t, J = 7.8 Hz, 2H),4.01 (s, 3H), 3.87 (s, 3H), 3.65 (s, 3H), 3.62-3.58 (m, 2H),3.20 (t, J = 7.8 Hz, 2H), 3.10 (t, J = 7.2 Hz, 2H); 13CNMR (125 MHz, CDCl3) δ 176.5, 156.4, 148.8, 137.9,133.2, 129.1, 128.5, 127.5, 118.8, 112.3, 110.9, 56.9, 56.7,53.5, 46.0, 34.1, 33.9, 26.1; LC/MS m/z 310.2 [M - I-];HRMS (FAB+) m/z calcd for C20H24NO2+ [M - I-]310.1802, found 310.1777.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

75
[ 4721-98-6 ]
[ 824-94-2 ]
[ 74-88-4 ]
6,7-dimethoxy-1-(4-methoxyphenethyl)-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; p-methoxybenzyl chloride; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 3h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 4h; chemoselective reaction;	6,7-Dimethoxy-1-(4-methoxyphenethyl)-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4b): A solutionof 1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg, 0.268 mmol), 4-methoxybenzyl chloride (57.8 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) in CH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 3 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0.0367 mmol) was added to the reaction mixture and stirred at rt. for 4 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted with DCM (2 × 25 mL). The combined organic layers weredried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gelcolumn chromatography using DCM/MeOH (9/1) as aneluent to afford 4b (69 mg, 0.15 mmol, 61%) as a yellowoil. 1H NMR (300 MHz, CDCl3) δ 7.13 (s, 1H), 7.02 (d,J = 8.4 Hz, 2H), 6.09 (s, 1H), 6.80 (d, J = 8.4 Hz, 2H),4.05 (t, J = 7.8 Hz, 2H), 4.01 (s, 3H), 3.87 (s, 3H), 3.77 (s,3H), 3.66 (s, 3H), 3.58 (t, J = 7.2 Hz, 2H), 3.19 (t,J = 7.8 Hz, 2H), 3.04 (t, J = 7.2 Hz, 2H); 13C NMR(125 MHz, CDCl3) δ 176.5, 158.9, 156.3, 148.8, 133.2,129.7, 129.6, 118.8, 114.4, 112.3, 110.9, 56.9, 56.7, 55.4,53.5, 46.1, 34.3, 33.2, 26.1; LC/MS m/z 340.2 [M - I-];HRMS (FAB+) m/z calcd for C21H26NO3+ [M - I-]340.1907, found 340.1915.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

76
[ 4721-98-6 ]
[ 352-11-4 ]
[ 74-88-4 ]
1-(4-fluorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; 1-chloromethyl-4-fluorobenzene; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 3h; chemoselective reaction;	1-(4-Fluorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4c): A solution of 1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 4-fluorobenzyl chloride (52.9 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d wascompletely consumed in 1 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0. 0367 mmol) was added to the reaction mixture and stirred at rt. for 3 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted withDCM (2 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gel column chromatography using DCM/MeOH (9/1) as aneluent to afford 4c (70 mg, 0.15 mmol, 63%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.18-7.12 (m, 2H),7.11 (s, 1H), 6.99-6.92 (m, 2H), 6.89 (s, 1H), 4.08 (t,J = 7.8 Hz, 2H), 4.00 (s, 3H), 3.86 (s, 3H), 3.77 (s, 3H),3.62 (t, J = 7.2 Hz, 2H), 3.22 (t, J = 7.5 Hz, 2H), 3.11 (t,J = 7.2 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 176.2,161.9 (d, 1JC-F = 244.9 Hz), 156.4, 148.7, 133.8, 130.2 (d,J = 7.7 Hz), 118.7, 115.8 (d, J = 21.3 Hz), 112.4, 110.9,57.0, 56.8, 53.4, 46.4, 34.0, 33.0, 26.1, 25.4; LC/MS m/z328.2 [M - I-]; HRMS (FAB+) m/z calcd for C20H23FNO2+[M - I-] 328.1707, found 328.1691.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

77
[ 4721-98-6 ]
[ 104-83-6 ]
[ 74-88-4 ]
1-(4-chlorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; 1-Chloro-4-(chloromethyl)benzene; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 2h; chemoselective reaction;	1-(4-Chlorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4d): A solutionof 1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 4-chlorobenzyl chloride (58.9 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 1 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0.0367 mmol) was added to the reaction mixture and stirred at rt. for 2 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted with DCM (2 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gelcolumn chromatography using DCM/MeOH (9/1) as aneluent to afford 4d (84 mg, 0.18 mmol, 73%) as a slightly yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.26 (d,J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 7.10 (s, 1H),6.88 (s, 1H), 4.09 (t, J = 7.7 Hz, 2H), 4.02 (s, 3H), 3.87 (s,3H), 3.79 (s, 3H), 3.63 (t, J = 7.3 Hz, 2H), 3.23 (t,J = 7.7 Hz, 2H), 3.12 (t, J = 7.4 Hz, 2H); 13C NMR(125 MHz, CDCl3) δ 176.2, 156.5, 148.7, 136.6, 133.3,133.2, 130.0, 129.1, 118.7, 112.4, 110.9, 56.9, 56.8, 53.5,46.4, 33.8, 33.1, 26.1; LC/MS m/z 344.8 [M - I-]; HRMS(FAB+) m/z calcd for C20H23ClNO2+ [M - I-] 344.1412,found 344.1393.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

78
[ 4721-98-6 ]
[ 824-98-6 ]
[ 74-88-4 ]
6,7-dimethoxy-1-(3-methoxyphenethyl)-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; m-methoxybenzyl chloride; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 3h; chemoselective reaction;	6,7-Dimethoxy-1-(3-methoxyphenethyl)-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4e): A solution of1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 3-methoxybenzyl chloride (57.3 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 1 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0. 0367 mmol) was added to the reaction mixture and stirred at rt. for 3 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted withDCM (2 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gel column chromatography using DCM/MeOH (9/1) as an eluent to afford 4e (73 mg, 0.15 mmol, 64%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.20 (t, J = 8.1 Hz,1H), 7.13 (s, 1H), 6.89 (s, 1H), 6.80-6.75 (m, 1H),6.70-6.67 (m, 2H), 4.08 (t, J = 7.8 Hz, 2H), 4.02 (s, 3H),3.88 (s, 3H), 3.78 (s, 3H), 3.71 (s, 3H), 3.64 (t, J = 7.2 Hz,3H), 3.22 (t, J = 7.8 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H); 13CNMR (125 MHz, CDCl3) δ 176.4, 160.0, 156.3, 148.6,139.5, 133.3, 130.1, 120.7, 118.8, 114.6, 112.5, 112.3,110.9, 56.9, 56.7, 55.5, 53.5, 46.1, 33.9, 33.8, 26.1; LC/MSm/z 340.2 [M - I-]; HRMS (FAB+) m/z calcd forC21H26NO3+ [M - I-] 340.1907, found 340.1902.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

79
[ 4721-98-6 ]
[ 456-42-8 ]
[ 74-88-4 ]
1-(3-fluorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; m-fluorobenzyl chloride; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 4h; chemoselective reaction;	1-(3-Fluorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4f): A solution of1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 3-fluorobenzyl chloride (52.9 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 1 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0.0367 mmol) was added to the reaction mixture and stirred at rt. for 4 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted with DCM (2 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gel column chromatography using DCM/MeOH (9/1) as an eluent to afford 4f (60 mg, 0.13 mmol, 54%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.29-7.18 (m, 1H),7.08 (s, 1H), 6.98-6.95 (m, 1H), 6.94-6.84 (m, 3H), 4.08(t, J = 7.8 Hz, 2H), 3.99 (s, 3H), 3.85 (s, 3H), 3.78 (s, 3H),3.63 (t, J = 7.2 Hz, 2H), 3.22 (t, J = 7.8 Hz, 2H), 3.12 (t,J = 7.2 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 176.1,162.8 (d,1JC-F = 245.8 Hz), 156.4, 148.7, 140.6, 140.5 (d,JC-F = 7.2 Hz), 133.3, 130.7 (d, JC-F = 8.3 Hz), 124.4 (d,JC-F = 2.7 Hz), 118.7, 115.4 (d, JC-F = 21.0 Hz), 114.2 (d,JC-F = 21.0 Hz), 112.2, 111.0, 56.9, 56.8, 53.5, 46.3, 33.7,33.4, 26.1; LC/MS m/z 328.2 [M - I-]; HRMS (FAB+) m/zcalcd for C20H23FNO2+ [M - I-] 328.1707, found328.1689.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

80
[ 4721-98-6 ]
[ 7035-02-1 ]
[ 74-88-4 ]
6,7-dimethoxy-1-(2-methoxyphenethyl)-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; o-Methoxybenzyl chloride; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 5h; chemoselective reaction;	6,7-Dimethoxy-1-(2-methoxyphenethyl)-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4g): A solution of1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 2-methoxybenzyl chloride (57.3 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 1 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0. 0367 mmol) was added to the reaction mixture and stirred at rt. for 5 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted withDCM (2 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gelcolumn chromatography using DCM/MeOH (9/1) as aneluent to afford 4g (43 mg, 0.092 mmol, 38%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.18 (t, J = 7.8 Hz,1H), 7.11 (s, 1H), 6.90 (s, 1H), 6.79-6.74 (m, 1H),6.69-6.66 (m, 2H), 4.07 (t, J = 7.5 Hz, 2H), 4.00 (s, 3H),3.86 (s, 3H), 3.77 (s, 3H), 3.70 (s, 3H), 3.62 (t, J = 7.2 Hz,2H), 3.21 (t, J = 7.5 Hz, 2H), 3.07 (t, J = 7.2 Hz, 2H); 13CNMR (125 MHz, CDCl3) δ 176.4, 160.0, 156.2, 148.7,139.5, 133.3, 130.1, 120.7, 118.8, 114.6, 112.4, 112.3,110.9, 56.9, 56.7, 55.5, 53.4, 46.1, 33.9, 26.1; LC/MS m/z341.2 [M - I-]; HRMS (FAB+) m/z calcd for C21H26NO3+[M - I-] 340.1907, found 340.1937.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

81
[ 4721-98-6 ]
[ 345-35-7 ]
[ 74-88-4 ]
1-(2-fluorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline; 2-fluorobenzyl chloride; methyl iodide With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h; Stage #2: With sodium iodide In acetonitrile at 20℃; for 4h; chemoselective reaction;	1-(2-Fluorophenethyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium chloride (4 h): A solutionof 1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 2-fluorobenzyl chloride (52.9 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 1 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0.0367 mmol) was added to the reaction mixture and stirred at rt. for 4 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted with DCM (2 x 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gel column chromatography using DCM/MeOH (9/1) as aneluent to afford 4 h (84 mg, 0.12 mmol, 49%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.32-7.31 (m, 1H),7.26-7.22 (m, 1H), 7.21 (s, 1H), 7.16-7.09 (m, 1H),7.05-6.99 (m, 1H), 6.84 (s, 1H), 4.14 (t, J = 7.8 Hz, 2H),4.02 (s, 3H), 3.91 (s, 6H), 3.58 (t, J = 7.5 Hz, 2H), 3.29 (t, J = 7.5 Hz, 2H), 3.06 (t, J = 7.5 Hz, 2H); 13C NMR(125 MHz, CDCl3) δ 175.8, 161.0 (d,1JC-F = 242.6 Hz),156.3, 148.7, 133.4, 131.1, 131.1 (d, J = 4.3 Hz), 129.5 (t,J = 8.1 Hz), 125.0-124.8 (m), 118.9, 115.6, 115.4, 111.9,110.8, 56.9, 56.4, 53.5, 46.1, 32.7, 27.6, 26.0; LC/MS m/z329.2 [M - I-]. HRMS (FAB+) m/z calcd for C20H23FNO2+[M - I-] 328.1707, found 328.1696.

Reference： [1]Achary, Raghavendra; Kim, Seulgi; Choi, Yuri; Mathi, Gangadhar Rao; Kim, Hyun Jin; Hwang, Jong Yeon; Kim, Pilho [Bulletin of the Korean Chemical Society, 2019, vol. 40, # 3, p. 270 - 278]

82
[ 4721-98-6 ]
[ 74-88-4 ]
[ 7306-46-9 ]
[ 20226-10-2 ]

Yield	Reaction Conditions	Operation in experiment
74%		A solution of1d (50.0 mg, 0.244 mmol), methyl iodide (37.3 mg,0.268 mmol), 5-(bromomethyl)-1.3-benzodioxole (68.3 mg,0.366 mmol), and DIPEA (34.9 mg, 0.268 mmol) inCH3CN (1.0 mL) was stirred at rt. When 1d was completely consumed in 2 h based on the analysis of TLCand LC/MS, NaI (5.5 mg, 0.0367 mmol) was added to the reaction mixture and stirred at rt. for 4 h. The crude mixture was quenched with 0.5 N HCl (aq) and extracted withDCM (2 × 25 mL). The combined organic layers weredried over anhydrous Na2SO4 and the solvent was removed under vacuum. The crude mixture was purified on silica gelcolumn chromatography using DCM/MeOH (9/1) as aneluent to afford 4h (90 mg, 0.18 mmol, 74%) as a slightly yellow solid. 1H NMR (300 MHz, CDCl3) delta 7.11 (s, 1H),6.89 (s, 1H), 6.80-6.72 (m, 2H), 6.61 (dd, J = 8.1, 2.0 Hz,1H), 4.07 (t, J = 7.8 Hz, 2H), 4.00 (s, 3H), 3.85 (s, 3H),3.82 (s, 6H), 3.75 (s, 3H), 3.63 (t, J = 7.1 Hz, 2H),3.26-3.16 (m, 3H), 3.07 (t, J = 7.1 Hz, 2H); 13C NMR(125 MHz, CDCl3) delta 176.5, 156.3, 149.2, 148.7, 148.2,133.2, 130.5, 120.4, 118.9, 112.4, 112.1, 111.4, 110.8,56.9, 56.7, 56.5, 56.0, 53.4, 46.3, 34.2, 33.5, 26.1; LC/MS m/z 370.1 [M - I-]; HRMS (FAB+) m/z calcd forC22H28NO4+ [M - I-] 370.2013, found 370.2045.

Reference： [1]Bulletin of the Korean Chemical Society,2019,vol. 40,p. 270 - 278

83
C₁₂H₁₆ClNO₂*ClH [ No CAS ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
1.54 g	With sodium hydroxide In water for 0.166667h;	Procedure for preparation of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (9) (CAS Number: 4721-98-6)⁴ To a round-bottomed flask were added N-(3,4-dimethoxyphenethyl)acetamide (8) (8 mmol, 1.78 g) and toluene (9 mL). The round-bottomed flask was equipped with a reflux condenser and capped with a rubber septum. The mixture was heated at 40 oC under stirring and anhydrous conditions. After that, POCl3 (19.2 mmol, 2.94 g, 1.8 mL) was added dropwise using syringe and needle. The rubber septum was substituted by a glass cap and the reaction mixture was refluxed under stirring for 2 h. Then, the mixture was cooled with an ice bath for 4 h. The solvent was evaporated under reduced pressure, affording an intermediate salt. Afterwards, the intermediate salt was dissolved in water (20 mL) and a 40% (w/v) aqueous solution of NaOH (20 mL) was added to the mixture, which was maintained under stirring for 10 min. The mixture was extracted with CHCl3 (3 × 40 mL). The organic phase was washed with distilled water (20 mL) and dried over MgSO4. After filtration, the solvent was evaporated under reduced pressure to afford the desired product 9. Yield: 1.54 g (94%); brownish solid; m.p. 102-103 oC (m.p. lit.5 100-102 oC); Rf = 0.38 (eluent: methanol); 1H NMR (300 MHz, CDCl3): δ 6.99 (s, 1H), 6.69 (s, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 3.63 (tq, J = 7.6, 1.4 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 2.37 (t, J = 1.4 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 163.6, 150.8, 147.3, 131.0, 122.4, 110.1, 108.9, 56.1, 55.9, 46.9, 25.6, 23.3; IR (KBr, cm-1): 2993.5, 2962.6, 2922.1, 1602.8, 1514.1, 1408.4, 1350.1, 1213.2, 1060.8; GC/MS (m/z, %): 205 (100.0), 190 (57.9) 174 (21.5), 160 (21.4), 147 (12.8), 132 (4.3).

Reference： [1]Corrêa, Bianca K.; Silva, Tamiris R.C.; Raminelli, Cristiano [Tetrahedron Letters, 2018, vol. 59, # 39, p. 3583 - 3585]

84
[ 79-24-3 ]
[ 120-20-7 ]
[ 4721-98-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	With polyphosphoric acid at 100℃;	11H-Indolo[3,2-c]isoquinolines 15a-f (general protocol) General procedure: A mixture containing 90 mg (0.5 mmol) of homoveratrylamine16, 1.5 mmol of nitroalkane 6a-f, and polyphosphoric acid (1.0 g, P2O5 content was 86%) was placed in an Erlenmeyer flaskand stirred at 100-120 C (100 C in the case of nitromethane (6a) and nitroethane (6b)) until complete consumption of the reactants (ca. 1.5 h, TLC monitoring). Then the reaction mixture was colled down to room temperature, diluted with water (40 mL),and neutralized with 20% aqueous ammonia (ca. 7 mL) to obtain alkaline medium. The resulted mixture was extracted with ethyl acetate (4×15 mL), solvents were evaporated in vacuo, and the product was isolated by column chromatography (ethanol-ethyl acetate, 1 : 101 : 1.5).

Reference： [1]Aksenov; Malyuga; Abakarov; Aksenov; Voskressensky; Aksenov [Russian Chemical Bulletin, 2019, vol. 68, # 5, p. 1047 - 1051][Izv. Akad. Nauk, Ser. Khim., 2019, # 5, p. 1047 - 1051,5]

85
[ 91-63-4 ]
[ 34989-82-7 ]
[ 4721-98-6 ]
(R)-2-methyl-1,2-dihydroquinoline [ No CAS ]
[ 84108-98-5 ]
(6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With C₂₀H₃₀Cl₄Ir₂*C₆₆H₇₅Cl₂N₉O₂₄; sodium formate at 25℃; for 16h;	1.2. General Procedure for Asymmetric Transfer Hydrogenation. General procedure: [IrCp*Cl2]2 (1% mol) and Van (4% mol) were dissolved in 1 mL of MES buer (MES 1.2 M,HCOONa 3 M, final pH 5) and stirred for 60 min at 25 °C. The substrate (final concentration 16 mM)was added to the catalyst solution. The reaction was stirred for 18 h at 25 °C. At the end of the reaction10 L of NaOH 10 N was added and the aqueous media was extracted with CH2Cl2 for Substrate 1and 2 and with ethyl acetate for Substrate 3. The organic layers were dried with anhydrous Na2SO4,filtered, and the solvent was removed under vacuum to be analyzed by HPLC equipped with a chiralcolumn determining conversion and enantiomeric excess.

Reference： [1]Facchetti, Giorgio; Pellegrino, Sara; Bucci, Raffaella; Nava, Donatella; Gandolfi, Raffaella; Christodoulou, Michael S.; Rimoldi, Isabella [Molecules, 2019, vol. 24, # 15]

86
[ 91-63-4 ]
[ 34989-82-7 ]
[ 4721-98-6 ]
(R)-2-methyl-1,2-dihydroquinoline [ No CAS ]
[ 84108-98-5 ]
[ 493-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	With C₂₀H₃₀Cl₄Ir₂*C₆₆H₇₅Cl₂N₉O₂₄; sodium formate In aq. acetate buffer at 25℃; for 18h;	1.2. General Procedure for Asymmetric Transfer Hydrogenation. General procedure: [IrCp*Cl2]2 (1% mol) and Van (4% mol) were dissolved in 1 mL of MES buer (MES 1.2 M,HCOONa 3 M, final pH 5) and stirred for 60 min at 25 °C. The substrate (final concentration 16 mM)was added to the catalyst solution. The reaction was stirred for 18 h at 25 °C. At the end of the reaction10 L of NaOH 10 N was added and the aqueous media was extracted with CH2Cl2 for Substrate 1and 2 and with ethyl acetate for Substrate 3. The organic layers were dried with anhydrous Na2SO4,filtered, and the solvent was removed under vacuum to be analyzed by HPLC equipped with a chiralcolumn determining conversion and enantiomeric excess.

Reference： [1]Facchetti, Giorgio; Pellegrino, Sara; Bucci, Raffaella; Nava, Donatella; Gandolfi, Raffaella; Christodoulou, Michael S.; Rimoldi, Isabella [Molecules, 2019, vol. 24, # 15]

87
[ 91-63-4 ]
[ 34989-82-7 ]
[ 4721-98-6 ]
[ 130973-57-8 ]
[ 493-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	With C₂₀H₃₀Cl₄Ir₂*C₆₆H₇₅Cl₂N₉O₂₄; sodium formate In aq. phosphate buffer at 25℃; for 18h;	1.2. General Procedure for Asymmetric Transfer Hydrogenation. General procedure: [IrCp*Cl2]2 (1% mol) and Van (4% mol) were dissolved in 1 mL of MES buer (MES 1.2 M,HCOONa 3 M, final pH 5) and stirred for 60 min at 25 °C. The substrate (final concentration 16 mM)was added to the catalyst solution. The reaction was stirred for 18 h at 25 °C. At the end of the reaction10 L of NaOH 10 N was added and the aqueous media was extracted with CH2Cl2 for Substrate 1and 2 and with ethyl acetate for Substrate 3. The organic layers were dried with anhydrous Na2SO4,filtered, and the solvent was removed under vacuum to be analyzed by HPLC equipped with a chiralcolumn determining conversion and enantiomeric excess.

Reference： [1]Facchetti, Giorgio; Pellegrino, Sara; Bucci, Raffaella; Nava, Donatella; Gandolfi, Raffaella; Christodoulou, Michael S.; Rimoldi, Isabella [Molecules, 2019, vol. 24, # 15]

88
[ 4721-98-6 ]
[ 108-24-7 ]
[ 65695-26-3 ]
[ 143261-75-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C₄₂H₄₆FeP₂; hydrogen bromide; hydrogen In tetrahydrofuran; water at 30℃; for 12h; Schlenk technique; Autoclave; Stage #2: acetic anhydride Schlenk technique; Autoclave;

Reference： [1]Nie, Huifang; Zhu, Yupu; Hu, Xiaomu; Wei, Zhao; Yao, Lin; Zhou, Gang; Wang, Pingan; Jiang, Ru; Zhang, Shengyong [Organic Letters, 2019, vol. 21, # 21, p. 8641 - 8645]

89
[ 108-30-5 ]
[ 4721-98-6 ]
5-(6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-ylidene)-4-oxopentanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Heating; Inert atmosphere;	General procedure for preparation of 25-28 General procedure: The corresponding 1-methyl or 1-ethyl-3,4-dihydroisoquinoline (19, 1 mmol, 0.205 g; 20, 1 mmol, 0.219 g) was dissolved in dry xylene (2 mL) and the corresponding anhydride (1.5 mmol) was added. The reaction mixture was heated under inert atmosphere for 6 hours. TLC was used to monitor the course of the reaction. After completion, the solvent was evaporated under reduced pressure and the resulting crude products were isolated and purified by means of column chromatography, followed by recrystallization.

Reference： [1]Burdzhiev, Nikola; Pashev, Aleksandar; Stanoeva, Elena [Beilstein Journal of Organic Chemistry, 2020, vol. 16, p. 1456 - 1464]

90
[ 108-55-4 ]
[ 4721-98-6 ]
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-ylidene)cyclohexane-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Heating; Inert atmosphere;	General procedure for preparation of 25-28 General procedure: The corresponding 1-methyl or 1-ethyl-3,4-dihydroisoquinoline (19, 1 mmol, 0.205 g; 20, 1 mmol, 0.219 g) was dissolved in dry xylene (2 mL) and the corresponding anhydride (1.5 mmol) was added. The reaction mixture was heated under inert atmosphere for 6 hours. TLC was used to monitor the course of the reaction. After completion, the solvent was evaporated under reduced pressure and the resulting crude products were isolated and purified by means of column chromatography, followed by recrystallization.

Reference： [1]Burdzhiev, Nikola; Pashev, Aleksandar; Stanoeva, Elena [Beilstein Journal of Organic Chemistry, 2020, vol. 16, p. 1456 - 1464]

91
[ 4480-83-5 ]
[ 4721-98-6 ]
4-(6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-ylidene)-2H-pyran-3,5(4H,6H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Heating; Inert atmosphere;	General procedure for preparation of 25-28 General procedure: The corresponding 1-methyl or 1-ethyl-3,4-dihydroisoquinoline (19, 1 mmol, 0.205 g; 20, 1 mmol, 0.219 g) was dissolved in dry xylene (2 mL) and the corresponding anhydride (1.5 mmol) was added. The reaction mixture was heated under inert atmosphere for 6 hours. TLC was used to monitor the course of the reaction. After completion, the solvent was evaporated under reduced pressure and the resulting crude products were isolated and purified by means of column chromatography, followed by recrystallization.

Reference： [1]Burdzhiev, Nikola; Pashev, Aleksandar; Stanoeva, Elena [Beilstein Journal of Organic Chemistry, 2020, vol. 16, p. 1456 - 1464]

92
[ 3261-87-8 ]
[ 4721-98-6 ]
(±)-trans-9,10-dimethoxy-11b-methyl-4-oxo-1,3,4,6,7,11b-hexahydro-[1,4]thiazino[3,4-a]isoquinoline-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Heating; Inert atmosphere;	General procedure for preparation of 25-28 General procedure: The corresponding 1-methyl or 1-ethyl-3,4-dihydroisoquinoline (19, 1 mmol, 0.205 g; 20, 1 mmol, 0.219 g) was dissolved in dry xylene (2 mL) and the corresponding anhydride (1.5 mmol) was added. The reaction mixture was heated under inert atmosphere for 6 hours. TLC was used to monitor the course of the reaction. After completion, the solvent was evaporated under reduced pressure and the resulting crude products were isolated and purified by means of column chromatography, followed by recrystallization.

Reference： [1]Burdzhiev, Nikola; Pashev, Aleksandar; Stanoeva, Elena [Beilstein Journal of Organic Chemistry, 2020, vol. 16, p. 1456 - 1464]

93
[ 4721-98-6 ]
N-tosyl-L-prolyl chloride [ No CAS ]
(S)-(6,7-dimethoxy-1-methylene-3,4-dihydroisoquinoline-2(1H)-yl) (1-tosylpyrrolidin-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine In dichloromethane at 0℃;	4.2.5. (S)-(6,7-Dimethoxy-1-methylene-3,4-dihydroisoquinoline-2(1H)-yl) (1-tosylpyrrolidin-2-yl)methanone (3) [17] To a round-bottomed flask were added 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (9) (205 mg, 1 mmol), (S)-1-tosylpyrrolidine-2-carbonyl chloride (11) (350 mg, 1.2 mmol), dichloromethane (10 mL), and dry triethylamine (0.21 mL,1.5 mmol). The round-bottomed flask was capped with a rubber septum. Then, the reaction was cooled to 0 °C and maintained under stirring for 1 h. Afterwards, the mixture was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate/hexane (1.25:0.75) as eluent, affording desired product 3. Yield: 0.40 g (88%); yellowish solid; m.p. 146-148 °C; Rf = 0.52 (eluent: ethyl acetate/hexane (1.25:0.75); [α]21D = -148.5° (c = 0.1 MeOH); 1H NMR (300 MHz, CDCl3, ppm): δ 7.47-7.44 (m, 2H), 7.11-7.08 (m, 2H), 7.01 (s, 1H) 6.53 (s, 1H), 5.50 (s, 1H), 4.93 (s, 1H), 4.89 (t, J = 7.8 Hz, 1H), 4.19-4.12 (m, 1H), 3.86 (s, 3H), 3.80 (s, 3H), 3.36-3.58 (m, 1H), 3.51-3.44 (m, 1H), 3.35-3.27 (m, 1H), 2.92-2.82 (m, 1H), 2.68-2.60 (m, 1H), 2.30 (s, 3H), 2.02-1.80 (m, 3H), 1.67-1.61 (m, 1H); 13C NMR (75 MHz, CDCl3, ppm): δ 200.2, 171.2, 150.0, 147.7, 143.1, 143.0, 135.6, 129.4, 127.5, 123.3, 111.4, 106.6, 104.4, 62.6, 57.4, 56.1, 55.9, 49.0, 31.9, 28.4, 24.9, 21.5; IR (KBr, cm-1) 3431.4, 3132.4, 2968.4, 2939.5, 2883.6, 1668.4, 1606.7, 1512.1, 1408.4, 1338.6, 1271.0, 1157.2, 1074.3; HRMS calculated for [C24H29N2O5S]+ 457.1792, found [C24H29N2O5S]+ 457.1799.

Reference： [1]Casagrande, Gleison A.; Deflon, Victor M.; Martins, Gabriel R.; Oliveira-Silva, Diogo; Perecim, Givago P.; Pinto, Leandro M. C.; Raminelli, Cristiano [Tetrahedron, 2020]

94
[ 4721-98-6 ]
[ 886-38-4 ]
8,9-dimethoxy-10b-methyl-2,3-diphenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	In acetonitrile at 82℃; for 1h;	5.10. Synthesis of 8,9-Dimethoxy-10b-methyl-2,3-diphenyl-5,6-dihydropyrrolo [2,1-a]isoquinolin-1-one (57ai) 6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline (0.0377 g, 0.1836 mmol) diphenylcyclopropenone (0.0250 g,0.1212 mmol) were dissolved in acetonitrile (5 mL). The flask heated at 82°C for 1 h, while continuously stirring. After heating,the solvent was removed in vacuo. The crude product was purifiedby silica column chromatography to give the product as a pale yellow solid (0.0296 g, 57% yield), m.p. 235-237°C. Rf 0.3 (ethylacetate/hexane, 4:6); 1H NMR (300 MHz, CDCl3)δ : 7.59 (1H, s, Ar),7.49e7.28 (5H, m, Ph), 7.10e7.06 (4H, m, Ph), 7.04e7.01 (1H, m, Ph),6.52 (1H, s, Ar), 4.00 (3H, s, OMe), 3.92 (1H, dd, J 10.2, 3.5 Hz,CHH), 3.84 (3H, s, OMe), 3.46 (1H, ddd, J 10.2, 10.2, 2.7 Hz, CHH),2.74e2.56 (1H, m, CHH), 2.49 (1H, dd, J 11.9,1.7 Hz, CHH),1.76 (3H,s, Me); 13C NMR (75 MHz, CDCl3) δ : 199.5 (C]O), 172.3 (qC), 148.2(qC), 147.9 (qC), 131.7 (qC), 130.9 (qC), 130.2 (CH), 129.1 (CH), 128.7(CH), 128.4 (qC), 128.2 (CH), 127.7 (CH), 125.3 (CH), 124.3 (qC), 113.4(qC),110.6 (CH),109.6 (CH), 67.9 (qC), 56.2 (OCH3), 55.9 (OCH3), 40.7(CH2), 29.8 (CH2), 26.4 (CH3). IR (neat, cm-1) νmax: 2937.2, 2835.0,2360.6, 2339.3, 1656.6, 1602.6, 1544.8, 1504.3, 1432.9, 1404.0,1344.2, 1324.9, 1259.4, 1230.4, 1207.3, 1124.4, 1080.0, 999.0, 773.4,732.90, 690.4, 640.3, 551.6. HRMS: [M+ H(+)] for C27H26NO3,calculated 412.1917, found 412.1913.

Reference： [1]Jamshaid, Faisal; Kondakal, Vishnu V.R.; Newman, C. Declan; Dobson, Rhianne; João, Heidi; Rice, Craig R.; Mwansa, Joseph M.; Thapa, Bimod; Hemming, Karl [Tetrahedron, 2020, vol. 76, # 45]

95
[ 4721-98-6 ]
[ 25361-94-8 ]
8,9-dimethoxy-10b-methyl-2,3-bis(4-methoxyphenyl)-5,6-dihydropyrrolo[2,1-a]isoquinolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	In chloroform; acetonitrile for 96h; Reflux;	5.11. Synthesis of 8,9-Dimethoxy-10b-methyl-2,3-bis(4-dimethoxyphenyl)-5,6-dihydropyrrolo[2,1-a]isoquinolin-1-one(57aii) 6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline [37] (0.029 g,0.141 mmol) and 2,3-bis(4-methoxyphenyl)cycloprop-2-en-1-one[35,36] (0.025 g, 0.094 mmol) were dissolved in a mixture of acetonitrile (2.5 mL) and chloroform (7.5 mL). The solution was heated at reflux for 96 h, with continuous stirring. The solvent was removed and the crude product was purified via silica columnchromatography to give the product as a bright yellow solid(0.024 g, 53% yield), m.p. 235-237° C. Rf 0.3 (ethyl acetate/hexane,11:9); 1H NMR (400 MHz, CDCl3) δ: 7.57 (s, 1H, Ar), 7.37e7.36 (2H,m, Ar), 7.01 (2H, d, J 8.6 Hz, Ar), 6.96 (2H, d, J 7.6 Hz, Ar), 6.68(2H, d, J 8.6 Hz, Ar), 6.50 (1H, s, Ar), 4.00 (3H, s, OMe), 3.95 (1H,overlapping m, CHH), 3.86 (3H, s, OMe), 3.82 (3H, s, OMe), 3.72 (3H,s, OMe), 3.47e3.40 (1H, m, CHH), 2.61 (1H, m, CHH), 2.46 (1H, d,J 14.4 Hz, CHH), 1.74 (3H, s, Me); 13C NMR (100 MHz, CDCl3) δ:199.6 (C]O), 171.7 (qC), 160.9 (qC), 157.2 (qC), 148.1 (qC), 147.8 (qC),129.7 (2 CH), 128.4 (qC), 124.5 (qC), 124.4 (qC), 122.9 (qC), 114.5(CH), 113.2 (CH), 113.1 (qC), 110.5 (CH), 109.7 (CH), 67.8 (qC), 56.1(OCH3), 55.8 (OCH3), 55.4 (OCH3), 55.1 (OCH3), 40.8 (CH2), 29.7(CH2), 26.3 (CH3); IR (neat, cm-1) ν max: 2929.5, 2833.1, 1652.8,1515.9, 1459.9, 1404.0, 1342.3, 1299.9, 1247.8, 1174.5, 1022.1, 919.9,829.3, 582.4, 549.6; HRMS: [M H] for C29H30NO5, calculated472.2126, found 472.2119.

Reference： [1]Jamshaid, Faisal; Kondakal, Vishnu V.R.; Newman, C. Declan; Dobson, Rhianne; João, Heidi; Rice, Craig R.; Mwansa, Joseph M.; Thapa, Bimod; Hemming, Karl [Tetrahedron, 2020, vol. 76, # 45]

96
[ 3757-06-0 ]
[ 4721-98-6 ]
[ 70474-51-0 ]