Home Cart 0 Sign in  

[ CAS No. 34598-49-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 34598-49-7
Chemical Structure| 34598-49-7
Structure of 34598-49-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 34598-49-7 ]

Related Doc. of [ 34598-49-7 ]

Alternatived Products of [ 34598-49-7 ]

Product Details of [ 34598-49-7 ]

CAS No. :34598-49-7 MDL No. :MFCD00082718
Formula : C9H7BrO Boiling Point : -
Linear Structure Formula :- InChI Key :KSONICAHAPRCMV-UHFFFAOYSA-N
M.W :211.06 Pubchem ID :520695
Synonyms :

Calculated chemistry of [ 34598-49-7 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.22
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 47.19
TPSA : 17.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.91 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.06
Log Po/w (XLOGP3) : 2.36
Log Po/w (WLOGP) : 2.58
Log Po/w (MLOGP) : 2.42
Log Po/w (SILICOS-IT) : 3.44
Consensus Log Po/w : 2.57

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.04
Solubility : 0.193 mg/ml ; 0.000914 mol/l
Class : Soluble
Log S (Ali) : -2.36
Solubility : 0.924 mg/ml ; 0.00438 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.98
Solubility : 0.0224 mg/ml ; 0.000106 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.66

Safety of [ 34598-49-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302+H312+H332-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 34598-49-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 34598-49-7 ]
  • Downstream synthetic route of [ 34598-49-7 ]

[ 34598-49-7 ] Synthesis Path-Upstream   1~45

  • 1
  • [ 34598-49-7 ]
  • [ 6941-75-9 ]
YieldReaction ConditionsOperation in experiment
92% With manganese(IV) oxide; ammonium hydroxide; oxygen; chlorobenzene In N,N-dimethyl-formamide at 100℃; for 24 h; Autoclave; Green chemistry General procedure: 0.01g of MnO2 catalyst, 0.5mmol of 1-indanone, 0.2g of ammonia water (25wtpercent) and 2g of chlorobenzene were added to a stainless steel autoclave with a polytetrafluoroethylene inner liner.The temperature was raised to 110 by automatic temperature controller, 0.6MPa oxygen was added and the reaction was continued for 4h. The pressure was kept constant during the reaction.The reaction product was analyzed using GC-MS with a phthalamide yield of 85percent.
Reference: [1] Patent: CN106278990, 2017, A, . Location in patent: Paragraph 0013; 0017; 0018; 0020; 0024; 0028
  • 2
  • [ 34598-49-7 ]
  • [ 20921-00-0 ]
Reference: [1] Chemistry - An Asian Journal, 2017, vol. 12, # 24, p. 3119 - 3122
  • 3
  • [ 34598-49-7 ]
  • [ 20921-00-0 ]
  • [ 1162262-43-2 ]
Reference: [1] European Journal of Organic Chemistry, 2009, # 15, p. 2526 - 2532
[2] European Journal of Organic Chemistry, 2009, # 15, p. 2526 - 2532
  • 4
  • [ 34598-49-7 ]
  • [ 34784-05-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 827 - 832
  • 5
  • [ 34598-49-7 ]
  • [ 557-21-1 ]
  • [ 25724-79-2 ]
Reference: [1] Journal of Medicinal Chemistry, 2000, vol. 43, # 9, p. 1670 - 1683
[2] Patent: US6369226, 2002, B1, . Location in patent: Page column 18
[3] Patent: US2009/75996, 2009, A1, . Location in patent: Page/Page column 21
  • 6
  • [ 34598-49-7 ]
  • [ 544-92-3 ]
  • [ 25724-79-2 ]
Reference: [1] Organic Letters, 2005, vol. 7, # 18, p. 3885 - 3888
[2] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 2, p. 371 - 385
[3] Canadian Journal of Chemistry, 1995, vol. 73, # 3, p. 307 - 318
[4] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 8, p. 1181 - 1184
[5] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
  • 7
  • [ 34598-49-7 ]
  • [ 25724-79-2 ]
YieldReaction ConditionsOperation in experiment
52% at 120℃; for 24 h; Inert atmosphere To a solution of 5-bromo-1-indanone (1) (0.5 g, 2.4 mmol) in DMF (1 mL), CuCN (0.25 g, 2.8 mmol) was added. The mixture was stirred at 120 °C for 24 h under argon atmosphere. Then the reaction mixture was cooled to r.t., diluted with CH2Cl2 (25 mL) and the solid generated was removed by vacuum filtration. The filtrate was washed with saturated solution of NH4Cl (2 .x. 20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtrated, and solvent was eliminated under reduced pressure. The residue obtained was purified by flash chromatography on silica gel (1:4 AcOEt:hexane) to give the titled compound (0.20 g, 52percent) as a slightly yellow solid. Mp: 131.5-132.8 °C. IR: 3059, 2224, 1710, 1608. 1H NMR (CDCl3) δ: 7.84 (s, 1H), 7.81 (d, 1H, J = 4.4), 7.64 (dd, 1H, J = 7.8, 0.7), 3.23-3.19 (m, 2H), 2.79-2.74 (m, 2H). Spectroscopic data were coincident with literature.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 9, p. 2670 - 2674
  • 8
  • [ 557-21-1 ]
  • [ 34598-49-7 ]
  • [ 25724-79-2 ]
Reference: [1] Patent: US2009/298894, 2009, A1, . Location in patent: Page/Page column 47
[2] Patent: WO2009/112275, 2009, A1, . Location in patent: Page/Page column 139
  • 9
  • [ 34598-49-7 ]
  • [ 25724-79-2 ]
Reference: [1] Patent: US6159996, 2000, A,
  • 10
  • [ 34598-49-7 ]
  • [ 25724-79-2 ]
YieldReaction ConditionsOperation in experiment
50% at 140℃; Step A:
1-Oxo-2,3-dihydro-1H-inden-5-carbonitrile
5-Bromo-2,3-dihydro-1H-inden-1-one (21.1 g, 100 mmol) and cupric cyanide (17.9 g, 200 mmol) were mixed in 200 ml of dimethylformamide and stirred overnight at 140 °C After the solution was cooled down to room temperature, 500 ml of ethyl acetate was added and the precipitate was removed by filteration using kieselguhr.
The solid was rinsed with ethyl acetate for several times.
The pooled filtrates were washed with 1 N hydrochloric acid twice and then with brine for 3 times, dried over anhydrous magnesium sulfate, filtered, and concentrated.
The crude product was purified on silica gel, eluting with ethyl acetate/hexanes (1:2), to obtain 7.9 g of the desired compound (50percent yield). MS(M+1)=158.05.
Reference: [1] Patent: EP2385035, 2011, A1, . Location in patent: Page/Page column 11-12
  • 11
  • [ 34598-49-7 ]
  • [ 25724-79-2 ]
Reference: [1] Patent: US6090833, 2000, A,
  • 12
  • [ 83-33-0 ]
  • [ 15115-60-3 ]
  • [ 14548-39-1 ]
  • [ 34598-49-7 ]
  • [ 103515-98-6 ]
Reference: [1] European Journal of Organic Chemistry, 2001, # 11, p. 2107 - 2114
  • 13
  • [ 83-33-0 ]
  • [ 15115-60-3 ]
  • [ 14548-39-1 ]
  • [ 34598-49-7 ]
Reference: [1] European Journal of Organic Chemistry, 2001, # 11, p. 2107 - 2114
  • 14
  • [ 34598-49-7 ]
  • [ 33065-61-1 ]
YieldReaction ConditionsOperation in experiment
52%
Stage #1: With sodium tetrahydroborate In methanol at 0℃; for 2 h; Inert atmosphere
Stage #2: With sulfuric acid In water; ethylene glycol at 75℃; for 2 h;
Sodium borohydride (1.1 g, 0.029 mol) was added, in 3 portions, to a solution of 5-bromo-indan-1-one (3.09 g, 0.0136 mol; CASNo. 34598-49-7) in methanol (25 ml_) at 00C under an atmosphere of argon. After 2 h, the reaction mixture was partitioned between EtOAc and water. The organic layer was separated, extracted with water, brine, dried (Na2SO4) and concentrated in vacuo to give an amber solid (3.16 g). This solid (1.58 g) was dissolved in ethylene glycol (63 ml_) and treated with 20percent vol. aq. sulfuric acid (63 ml_). The reaction mixture was heated to 75 0C for 2 hours then cooled to room temperature and extracted with DCM (2x). The combined organic layers were extracted with saturated aq. NaHCO3, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by silica gel column eluted with hexanes to afford 4a (0.76 g, 52percent) as a clear liquid.
46%
Stage #1: With sodium tetrahydroborate In methanol at 0 - 20℃; for 1.66667 h;
Stage #2: With toluene-4-sulfonic acid In benzene for 1 h; Reflux; Dean-Stark
To an ice cooled mixture of commercially available 5-bromo-1-indanone (20mmol) in MeOH (50mL) was added sodium borohydride (10mmol). After stirring for 10min the mixture was allowed to warm to rt. The mixture was stirred for 1.5h and then concentrated under vacuum. The residue was dissolved in EtOAc, washed with 1N NaOH and brine, dried over MgSO4 and then concentrated under vacuum. The residue was dissolved in benzene (50mL) and 4-toluenesulfonic acid monohydrate (0.1mmol) was added. The mixture was heated to reflux for 1h using Dean-Starks trap. Once cooled the reaction solution was washed with water, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography to afford the title compound. Yield 46percent, clear oil. 1H NMR (400MHz, CDCl3) δ 7.60 (s, 1H), 7.41 (dd, J=8.1, 2.0Hz, 1H), 7.26 (d, J=8.0Hz, 1H), 6.84 (d, J=5.4Hz, 1H), 6.55 (d, J=5.6Hz, 1H), 3.39 (s, 2H). 13C NMR (101MHz, CDCl3) δ 145.8, 143.8, 134.6, 131.5, 129.3, 127.0, 122.1, 118.7, 39.1.
Reference: [1] Patent: WO2009/67202, 2009, A1, . Location in patent: Page/Page column 195
[2] European Journal of Medicinal Chemistry, 2017, vol. 141, p. 101 - 112
[3] Organic and Biomolecular Chemistry, 2003, vol. 1, # 8, p. 1298 - 1307
[4] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 827 - 832
[5] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 12, p. 1657 - 1662
[6] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 1793 - 1802
[7] Patent: US2003/92743, 2003, A1,
[8] Tetrahedron, 2010, vol. 66, # 44, p. 8557 - 8561
  • 15
  • [ 34598-49-7 ]
  • [ 33065-61-1 ]
  • [ 75476-78-7 ]
Reference: [1] Tetrahedron Letters, 2005, vol. 46, # 8, p. 1353 - 1356
  • 16
  • [ 34598-50-0 ]
  • [ 34598-49-7 ]
YieldReaction ConditionsOperation in experiment
92% With tert.-butylhydroperoxide In water at 100℃; for 24 h; General procedure: Caution. tert-Butyl hydroperoxide is an exceptionally dangerous chemical that is highly reactive, flammable, and toxic. It is corrosive to skin and mucous membranes and causes respiratory distress when inhaled. A solution of secondary alcohol (1 mmol) and 70percent TBHP (6 or 10 equiv.) was stirred at 100 °C for 24 h. The reaction mixture was quenched with the saturated solution of sodium thiosulfate (5 mL) and extracted with dichloromethane (3 x 10 mL). The combined dichloromethane extracts were dried over anhydrous Na2SO4 and filtered, and then the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE or PE/EtOAc as the eluent to obtain the desired products.
Reference: [1] Synthetic Communications, 2016, vol. 46, # 21, p. 1747 - 1758
  • 17
  • [ 31736-73-9 ]
  • [ 34598-49-7 ]
Reference: [1] Patent: US5332757, 1994, A,
[2] Journal of Materials Chemistry, 2012, vol. 22, # 10, p. 4483 - 4490
[3] Chemical Communications, 2016, vol. 52, # 56, p. 8757 - 8760
  • 18
  • [ 42287-90-1 ]
  • [ 34598-49-7 ]
  • [ 125114-77-4 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 389 - 395
[2] Tetrahedron, 2007, vol. 63, # 2, p. 389 - 395
  • 19
  • [ 335159-82-5 ]
  • [ 34598-49-7 ]
Reference: [1] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
[2] Journal of Chemical Research, Miniprint, 1996, # 1, p. 301 - 315
  • 20
  • [ 83-33-0 ]
  • [ 15115-60-3 ]
  • [ 14548-39-1 ]
  • [ 34598-49-7 ]
  • [ 103515-98-6 ]
Reference: [1] European Journal of Organic Chemistry, 2001, # 11, p. 2107 - 2114
  • 21
  • [ 42287-90-1 ]
  • [ 34598-49-7 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1983, vol. 2, # 3-4, p. 96 - 104
[2] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
  • 22
  • [ 140184-19-6 ]
  • [ 34598-49-7 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 389 - 395
  • 23
  • [ 83-33-0 ]
  • [ 15115-60-3 ]
  • [ 14548-39-1 ]
  • [ 34598-49-7 ]
Reference: [1] European Journal of Organic Chemistry, 2001, # 11, p. 2107 - 2114
  • 24
  • [ 15852-73-0 ]
  • [ 34598-49-7 ]
Reference: [1] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
  • 25
  • [ 107558-73-6 ]
  • [ 34598-49-7 ]
Reference: [1] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
  • 26
  • [ 125115-01-7 ]
  • [ 34598-49-7 ]
Reference: [1] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
  • 27
  • [ 932-77-4 ]
  • [ 34598-49-7 ]
Reference: [1] Russian Journal of Organic Chemistry, 2002, vol. 38, # 12, p. 1769 - 1774
  • 28
  • [ 3650-77-9 ]
  • [ 34598-49-7 ]
Reference: [1] Chemical Communications, 2013, vol. 49, # 33, p. 3470 - 3472
  • 29
  • [ 151583-29-8 ]
  • [ 34598-49-7 ]
Reference: [1] Chemical Communications, 2013, vol. 49, # 33, p. 3470 - 3472
  • 30
  • [ 2039-86-3 ]
  • [ 34598-49-7 ]
Reference: [1] Angewandte Chemie - International Edition, 2015, vol. 54, # 43, p. 12683 - 12686[2] Angew. Chem., 2015, vol. 127, # 43, p. 12874 - 12877,4
  • 31
  • [ 108-86-1 ]
  • [ 34598-49-7 ]
Reference: [1] Chemical Communications, 2016, vol. 52, # 56, p. 8757 - 8760
  • 32
  • [ 3132-99-8 ]
  • [ 141-82-2 ]
  • [ 34598-49-7 ]
Reference: [1] Journal of Organic Chemistry, 1999, vol. 64, # 1, p. 120 - 125
  • 33
  • [ 34598-49-7 ]
  • [ 34598-50-0 ]
YieldReaction ConditionsOperation in experiment
100% With sodium tetrahydroborate In ethanol at 60℃; for 0.1 h; A mixture of 5-bromo-2,3-dihydroinden-1-one (47.1) (23.7 mmol) and NaBH4 (47.4 mmol) in EtOH (50 mL) was stirred at 60° C. for 6 minutes. After evaporation of the solvent, the residue was purified by chromatography (silica gel; 1:2 EtOAc/hexane) providing compound 47.2 in 100percent yield. MS ESI (pos.) M/E: 195.0, 197.1 (M+H-H2O).
98%
Stage #1: at 20℃; for 1 h;
Stage #2: With water In ethyl acetate
[001033] Example 69. Preparation of N-(5-(3-terf-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)- 2-methoxyphenyl)-2,3-dihydro-lH-inden-l-yl)methanesulfonamide (compound IB-LO-2.44).; [001034] Part A. Preparation of 5-bromo-2,3-dihydro-lH-inden-l-ol.; [001035] A suspension of 5-bromo-2,3-dihydro-lη-inden-l-one (2.07g, 9.81mmol) in ethanol (49mL) was treated with the sodium borohydride (186mg, 4.90mmol) all at once. After a few minutes, the solution warmed slightly and all solids dissolved. After stirring at room temperature for Ih, the mixture was concentrated in vacuo to remove ethanol. The gum obtained was partitioned between ethyl acetate and water. The organic layer was extracted with saturated sodium bicarbonate solution (2 x) and saturated sodium chloride solution. Drying (Na2SO4) and concentration in vacuo afforded the title compound (3.05g, 98percent) as a colorless oil, which crystallized upon pumping under high vacuum <n="188"/>overnight.
98% With sodium tetrahydroborate In methanol at 0 - 20℃; for 0.75 h; 5-Bromo-indan-l-ol (15-2).; NaBH4 (350 mg, 9.25 mmol) was added to an ice cold solution of ketone 15-1 (1.632 g, 7.73 mmol) in methanol (15 mL). The reaction was allowed to warm to room temperature and after 45 min., 50 mL 1 M HCl was added. The resulting mixture was extracted with ethyl acetate (3 x 60 mL) and the combined ethyl acetate solution was washed with brine. The solution was then dried (Na2SO4), filtered and evaporated. The residue was purified by flash chromatography on silica gel (25percent ethyl acetate/hexanes) to give 15-2 (1.607 g, 98percent).
97% With sodium tetrahydroborate In tetrahydrofuran; methanol at 20℃; for 1 h; 5-Bromo-indanone (4 g, 19 MMOL) was dissolved in THF (50 ML) and MeOH (1 mL), and was reacted with NaBH4 (1.4 g, 37 MMOL) at rt for 1 h. EtOAc (50 mL) was added to dilute the reaction. The reaction mixture was washed with brine (80 ML). The organic layer was dried over NA2SO4 and then concentrated to dryness to give 3.9 g (97percent) of compound B as a white solid.
97% With sodium tetrahydroborate In methanol at 0 - 25℃; Commercially available 5-bromoindanone (5.1 g, 24.3 mmol) was diluted into methanol (150 mL), cooled to 0 0C, and treated with sodium borohydπde (1.8 g, 48.6 mmol). The reaction mixture was warmed to room temperature, aged overnight, and then partitioned between water and methylene chloride, the organic phase separated, dried and concentrated in vacuo. The clean crude alcohol (5.0 g, 97percent) was isolated and used in the next step without purification. This hydroxybromoindane (5.04 g, 23.6 mmol) was diluted into toluene (100 mL), treated with catalytic p-toluenesulfomc acid (400 mg), and the reaction mixture refluxed under Dean-Stark trap conditions for 6 h. The mixture was cooled to room temperature, extracted with saturated aqueous sodium bicarbonate, and the organic phase separated, dπed and concentrated in vacuo. The clean crude bromoindene (4.6 g, 100percent) was isolated as an oil and used in the next step without purification. This bromoindene (4.5 g) was diluted into (1 : 1) methanol-methylene chloride (150 mL), chilled to -78 0C, and treated with ozone for 30 minutes, removed from the ozonator, warmed to room temperature, and treated with solid sodium bicarbonate (2.5 g) and dimethylsulfide (3 mL). The reaction mixture was aged for 14 h, treated with 78percent ammonium hydroxide in water (30 mL), and the mixture maintained at room temperature overnight. The reaction mixture was then concentrated in vacuo, re-dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate, and the organic phase separated, dried and concentrated in vacuo. The crude product was purified by flash column chromatography (Biotage, SiO2, 20percent EtOAc-heptane) to provide the solid bromoisoqumolme. EXAMPLE 59 was prepared from this bromoisoqumohne by first Heck coupling in a similar manner as described in EXAMPLE 53 above and illustrated in Scheme 8. The resultant lsoquinohne acrylamide methyl ester intermediate was saponified with LiOH, and the acid reduced with p-toluenesulfonyl hydrazide, both in a similar manner as described in the examples above to provide the desired product. LCMS m/z 321 (M++ 1)
93% for 2 h; Step A:
5-Biomo-2,3-dihydro-1H-inden-1-ol
5-Bromo-2,3-dihydro-1H-inden-1-one (210 g, 1000 mmol) was suspended in 1 L methanol, and sodium borohydride (41.6 g, 1100 mmol) was added gradually within about 1 hour with stirring.
The solvent was removed at 50 °C under reduced pressure after being stirred for another 1 hour.
Ethyl acetate (1 L) was added followed by saturated sodium bicarbonate solution (500 mL).
After being stirred for some time, the solution was transferred to a separatory funnel and the aqueous phase was removed, The organic phase was washed with saturated sodium bicarbonate solution twice and with brine twice, dried (magnesium sulfate) and finally concentrated to obtain 198 g (93percent) of the subtitle compound.
92% With sodium tetrahydroborate In methanol at 20℃; for 0.5 h; 5-bromoindanone (1g, 5 mmol) was dissolved in methanol (30 mL). Add sodium borohydride (2 g, 50 mmol), Stir at room temperature for 30 minutes. The reaction solution was concentrated to dryness. Purified by silica gel column chromatography, A colorless liquid (0.92 g, 92percent) was obtained.
90% at 20℃; for 24 h; 5-bromo-2,3-dihydro-lH-inden-l-ol. To a solution of 5-bromo-2,3-dihydroinden-l- one (1.1 g, 5.2 mmol) in ethanol (100 mL) was added sodium borohydride (218 mg, 5.7 mmol). The mixture was stirred at room temperature for 24 hours. Then the resultant mixture was filtered. The filtrate was acidified with hydrochloric acid aqueous solution (IN) and the solvent was removed in vacuo. The residue was taken up with water (50 mL) and extracted with dichloromethane (50 mL). The combined organic phase was dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 4: 1) to give 5-bromo-2,3-dihydro-lH-inden-l-ol (1 g, 90percent) as a yellow oil. LRMS (M + H+) mlz: calcd 211.98; found 211. 1H NMR (300MHz, CDC13): δ 7.40 (s, 1H), 7.37 (d, J= 7.8 Hz, 1H), 7.27 (d, J= 7.8 Hz, 1H), 5.22-5.18 (m, 1H), 3.09-2.99 (m, 1H), 2.86-2.76 (m, 1H), 2.55-2.46 (m, 1H), 2.01-1.76 (m, 1H), 1.75 (s, 1H).
90% at 20℃; for 24 h; To a solution of 5-bromo-2,3-dihydroinden-1-one (1.1 g, 5.2 mmol) in ethanol (100 mL) was added sodium borohydride (218 mg, 5.7 mmol). The mixture was stirred at room temperature for 24 hours. Then the resultant mixture was filtered. The filtrate was acidified with hydrochloric acid aqueous solution (1N) and the solvent was removed in vacuo. The residue was taken up with water (50 mL) and extracted with dichloromethane (50 mL). The combined organic phase was dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=4:1) to give 5-bromo-2,3-dihydro-1H-inden-1-ol (1 g, 90percent) as a yellow oil. LRMS (M+H+) m/z: calcd 211.98. found 211. 1H NMR (300 MHz, CDCl3): δ 7.40 (s, 1H), 7.37 (d, J=7.8 Hz, 1H), 7.27 (d, J=7.8 Hz, 1H), 5.22-5.18 (m, 1H), 3.09-2.99 (m, 1H), 2.86-2.76 (m, 1H), 2.55-2.46 (m, 1H), 2.01-1.76 (m, 1H), 1.75 (s, 1H).
86%
Stage #1: With sodium tetrahydroborate In methanol at 0 - 20℃; for 1.5 h;
Stage #2: With water; ammonium chloride In methanol
Preparation 17: 5-formylindan-l-ol Step A: 5-bromoindan-l-ol5-bromo-l-indanone (300 mg, 1.42 mmol) was dissolved in 50 mL of methanol, and the mixture was cooled to 0°C, followed by addition of sodium borohydride (65 mg, 1.7 mmol). After stirring for 30 min, an ice bath was removed and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with ethyl acetate and a saturated ammonium chloride aqueous solution. The organic layer was taken, dried over anhydrous <n="40"/>magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to afford the title compound (260 mg, 86percent).
79%
Stage #1: With sodium tetrahydroborate In tetrahydrofuran at 20℃; for 0.5 h;
Stage #2: With water In tetrahydrofuran
To a stirred solution of compound XI-1 (2.5 g, 11.8 mmol) in THF (30 mL) was added NaBH4 (900 mg, 23.6 mmol), the mixture was stirred at rt. for 30 min. The reaction was quenched with water, and extracted with EtOAc (50 mL x 3). The organic layer was separated, dried over Na2S04, filtered and concentrated to give desired product XI-2 (2.0 g, yield 79percent), which was used for next step without further purification.
78% With dimethyl sulfide borane; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole In dichloromethane at -75 - 20℃; Inert atmosphere; Cooling with acetone-dry ice ΓΑ1 (R)-5-Bromo-indan-l-ol and (S)-5-bromo-indan-l-ol[S]-l-Methyl-3,3-diphenylhexahydropyrrolo[l,2-c][l,3,2]oxazaborole (7.11 ml, 7.11 mmol, eq: 0.15) was dissolved in CH2CI2 (200 ml), borane-methyl sulfide complex (3.96 g, 4.95 ml, 52.1 mmol) was added with intense stirring and the solution was cooled to -70 °C. Subsequently, a solution of 5-bromo-indan-l-one (10.0 g, 47.4 mmol) in CH2CI2 (50.0 ml) was added drop by drop (0.5 ml / min.) below - 75 °C. The reaction mixture was then warmed up to RT over night very slowly in a C Vacetone bath. Now, cold water (50 ml) was added slowly (foaming) and the reaction mixture was extracted twice with CH2CI2. The organic layers were dried over MgS04, filtered and concentrated in vacuo to give a crude product (10.786 g) which was purified by flash chromatography (silica gel, 100 g, 0percent to 50percent EtOAc in heptane) to give enriched title compound (9.716 g, R:S = 88: 12). This mixture was subsequently separated by HPLC chromatography (Chiralpak AD HPLC column, 5percent EtOH in heptane) to give (R)-5-bromo-indan-l-ol, [a]D (20 deg) = - 4.288, (c = 1.259 in MeOH) (7.83 g, 78percent) and (S)-5-bromo-indan-l-ol, [a]D (20 deg) = + 4.294, (c = 1.025 in MeOH) (1.16 g, 12percent), both as light yellow solids.
2.0 g With sodium tetrahydroborate In methanol at 20℃; for 14 h; 5-bromo-2,3-dihydro-1H-inden-1-one (2.0 g) was dissolved in methanol (20 mL), and to the resultant solution, sodium borohydride (0.54 g) was added at room temperature, followed by stirring the resultant reaction mixture at room temperature for 14 hours. To the reaction mixture, 1M hydrochloric acid (50 mL) was added, followed by extracting the resultant reaction mixture with ethyl acetate (50 mL) three times, and the organic phase was washed sequentially with water (50 mL) and a saturated saline (50 mL) and was dried over anhydrous sodium sulfate. From the organic phase, the solvent was distilled off under reduced pressure to obtain the subject compound (2.0 g) as a pale yellow solid.
4.8 g With sodium tetrahydroborate In methanol for 1 h; 5-bromo-indan-1-one (5 g, 23.8 mmol) was suspended in 100 ml of methanol. Sodium borohydride (1 g, 26.4 mmol) was slowly added with stirring and the addition was complete in about 10 minutes. After stirring for an additional hour, the solvent was removed under reduced pressure. Add 100 ml of ethyl acetate and add 100 ml of saturated sodium bicarbonate solution. After stirring for 30 minutes, the aqueous phase was removed with a separatory funnel, and the organic phase was washed twice with saturated brine, dried over anhydrous sodium sulfate and concentrated to give 4.8 g of the title compound.

Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 827 - 832
[2] Patent: US2007/66647, 2007, A1, . Location in patent: Page/Page column 69
[3] ACS Medicinal Chemistry Letters, 2010, vol. 1, # 9, p. 483 - 487
[4] Patent: WO2009/39134, 2009, A1, . Location in patent: Page/Page column 186-187
[5] Patent: WO2006/63179, 2006, A1, . Location in patent: Page/Page column 48
[6] Patent: WO2004/48322, 2004, A1, . Location in patent: Page 37
[7] Patent: WO2006/52555, 2006, A2, . Location in patent: Page/Page column 31; 66-67
[8] Patent: EP2385035, 2011, A1, . Location in patent: Page/Page column 13-14
[9] Patent: CN108341814, 2018, A, . Location in patent: Paragraph 0096-0097; 0099-0101
[10] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 1793 - 1802
[11] Organic and Biomolecular Chemistry, 2003, vol. 1, # 8, p. 1298 - 1307
[12] Patent: WO2013/75083, 2013, A1, . Location in patent: Paragraph 00312; 00313
[13] Patent: US9206128, 2015, B2, . Location in patent: Page/Page column 157; 158
[14] Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 651 - 664
[15] Patent: WO2009/38411, 2009, A2, . Location in patent: Page/Page column 38-39
[16] Patent: WO2013/25733, 2013, A1, . Location in patent: Paragraph 0463
[17] Patent: WO2012/101011, 2012, A2, . Location in patent: Page/Page column 46
[18] Patent: WO2005/63239, 2005, A1, . Location in patent: Page/Page column 137
[19] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 12, p. 1657 - 1662
[20] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 3, p. 547 - 551
[21] Journal of Medicinal Chemistry, 2005, vol. 48, # 5, p. 1563 - 1575
[22] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 1796 - 1805
[23] Patent: US2005/261310, 2005, A1, . Location in patent: Page/Page column 19
[24] Patent: EP1157047, 2003, B1,
[25] Patent: US2007/66647, 2007, A1, . Location in patent: Page/Page column 48
[26] Patent: WO2005/44195, 2005, A2, . Location in patent: Page/Page column 40-41
[27] Patent: US2007/219251, 2007, A1, . Location in patent: Page/Page column 19
[28] Patent: US2012/277150, 2012, A1, . Location in patent: Paragraph 0860
[29] Patent: WO2014/89324, 2014, A1, . Location in patent: Paragraph 0176
[30] Advanced Synthesis and Catalysis, 2015, vol. 357, # 11, p. 2540 - 2546
[31] Patent: JP5653442, 2015, B2, . Location in patent: Paragraph 0326-0327
[32] Patent: CN103130791, 2016, B, . Location in patent: Paragraph 0128-0130
[33] Patent: CN104016979, 2017, B, . Location in patent: Paragraph 0368; 0369
[34] Journal of Organic Chemistry, 2018, vol. 83, # 1, p. 452 - 458
[35] Patent: US5338740, 1994, A,
[36] Patent: WO2005/44195, 2005, A2, . Location in patent: Page/Page column 40-41
  • 34
  • [ 34598-49-7 ]
  • [ 75476-86-7 ]
Reference: [1] Organic and Biomolecular Chemistry, 2003, vol. 1, # 8, p. 1298 - 1307
  • 35
  • [ 34598-49-7 ]
  • [ 3470-45-9 ]
Reference: [1] Patent: WO2009/112275, 2009, A1,
[2] Journal of Medicinal Chemistry, 2018,
  • 36
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 34598-49-7 ]
  • [ 68634-02-6 ]
YieldReaction ConditionsOperation in experiment
74% With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 70℃; for 48 h; A pressure vessel was charged with 5-bromo-2,3-dihydro-l H-inden-l-one (30 g, 142 mmol), methanol (400 mL), DMF (400 mL), triethylamine (72 g, 0.71 mol), diacetoxypalladium (3.2 g, 14 mmol) and l,3-bis(diphenylphosphino)propane (1 1.7 g, 24 mmol). The sealed vessel was pressurized with carbon monoxide at 50 Psi and heated at 70 °C for 48 h. The vessel was cooled and the reaction mixture was filtered through CELITE and rinsed with MeOH (500 mL). The combined filtrates were concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (petroleum ether: EtOAc=3: l) to afford methyl l-oxo-2,3-dihydro-l H-indene-5-carboxylate (20 g, 74percent) as a yellow solid. MS ESI calc'd. For Cu H10O3 [M + H] + 191, found 191.
67% at 10℃; for 24 h; Into a 1-L round-bottom flask was placed a solution of 5-bromo-2,3-dihydro-lH- inden-l-one (30 g, 142 mmol, 1 equiv) in MeOH (450 mL), Pd(dppf)Cl2(15.6 g, 21.32 mmol, 0.15 equiv) and Et3N (57.5 g, 568 mmol, 4 equiv). CO (g) was introduced to the flask. The reaction mixture was stirred for 24 h at 100 °C in an oil bath, then cooled to room temperature. The solids were filtered and the filtrate was concentrated under vacuum. The residue was purified by normal phase chromatography on silica gel using EtOAc/petroleum ether (1:10). The collected fractions were concentrated under vacuum to afford 18 g (67percent yield) of the title compound as a yellow solid.
Reference: [1] Journal of Medicinal Chemistry, 2018,
[2] Patent: WO2014/74422, 2014, A1, . Location in patent: Paragraph 00201
[3] Patent: WO2017/218950, 2017, A1, . Location in patent: Paragraph 00325
[4] Patent: US2007/49603, 2007, A1, . Location in patent: Page/Page column 51
  • 37
  • [ 34598-49-7 ]
  • [ 33065-61-1 ]
  • [ 75476-78-7 ]
Reference: [1] Tetrahedron Letters, 2005, vol. 46, # 8, p. 1353 - 1356
  • 38
  • [ 34598-49-7 ]
  • [ 75476-78-7 ]
Reference: [1] Organic and Biomolecular Chemistry, 2003, vol. 1, # 8, p. 1298 - 1307
  • 39
  • [ 42287-90-1 ]
  • [ 34598-49-7 ]
  • [ 125114-77-4 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 389 - 395
[2] Tetrahedron, 2007, vol. 63, # 2, p. 389 - 395
  • 40
  • [ 34598-49-7 ]
  • [ 723760-74-5 ]
YieldReaction ConditionsOperation in experiment
51% at -15 - -10℃; for 4.5 h; Fuming nitric acid (166 ml) is cooled TO-15°C, and 5-bromoindan-1-one (25 g, 0.118 mol) is then added portionwise. After stirring for 4 hours 30 minutes at BETWEEN-10°C AND-15°C, the reaction mass is poured into ice-cold water (1600 ML). The precipitate is filtered off by suction, washed with water and taken up in dichloromethane to be dried over NA2SO4. The evaporation residue (25.8 g) is purified by crystallisation from ethanol (15.3 g, yield : 51percent). m. p. = 130°C 1H NMR-CDCI3-6 (ppm): 2.75-2. 82 (m, 2H); 3.18-3. 25 (m, 2H); 7.89 (s, 1H); 8.10 (s, 1H).
2.8 g at -15 - -10℃; for 4 h; Inert atmosphere Fuming nitric acid (25 mL) was cooled to -15° C. and 5-bromoindan-1-one (3.5 g, 0.0165 mol) was then added portionwise.
The reaction mixture was stirred at -10° C. under nitrogen atmosphere for 4 h.
The reaction was monitored by TLC and LCMS.
After completion of reaction, the mixture was poured into ice cold water (100 mL) and extracted with EtOAc (2*200 mL), the organic layer was washed with aq. sodium bicarbonate solution (2*100 mL) and finally brine solution washed (50 mL).
The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude compound that was dissolved in DCM (15 mL) and n-pentane (150 mL) was added.
The precipitated compound was filtered and dried under vacuum to obtain 5-bromo-6-nitro-indan-1-one (2.8 g) as a light brown solid.
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 41, p. 7753 - 7756
[2] Patent: WO2004/63148, 2004, A1, . Location in patent: Page 51
[3] Patent: US2018/51013, 2018, A1, . Location in patent: Paragraph 0694; 0695
  • 41
  • [ 34598-49-7 ]
  • [ 147497-32-3 ]
YieldReaction ConditionsOperation in experiment
61%
Stage #1: With sodium azide; methanesulfonic acid In dichloromethane at 0℃;
Stage #2: With sodium hydroxide In dichloromethane; water
Example 2 Methanesulfonic acid (31 mL, 10 equiv) was added to a mixture of the bromoindanone (10 g, 47 mmol) in CH2Cl2 (75 mL) at 0° C. Sodium azide was added slowly in portions to this mixture. After the sodium azide addition was complete, the mixture was stirred for an additional 30 min, and an aqueous mixture of NaOH (20 wt percent) was added until the mixture was slightly basic. The mixture was extracted with methylene chloride, and the combined organic layers were evaporated under reduced pressure. Purification of the mixture by flash column chromatography on silica gel (0percent to 50percent EtOAc/Hexanes then 0percent to 7percent MeOH/CH2Cl2) provided the desired product (6.5 g, 61percent).
47% With sodium azide In methanesulfonic acid; dichloromethane at 0 - 20℃; General Procedure: To an ice-cooled solution of the benzocycloketone (1.4 mmol) in 1:1 CH2Cl2/methanesulfonic acid (10 mL) (except for compound 17, where concentrated HCl was used as solvent), sodium azide (0.2g, 2.8 mmol) was added in portions. The resulting mixture was allowed to stir at 0 °C for 1h, and then warmed up to room temperature while stirring overnight. Then, the reaction mixture was poured into ice-water (20 mL), basified with 5M NaOH (aq) until pH 9, and extracted with CH2Cl2 (3 .x. 10 mL). The organic layers were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the crude lactam. Purification on silicagel chromathography (1:1 AcOEt/Hexane --> AcOEt) provided the desired 2H-benzolactam. The isomeric 1H benzolactam was also isolated in lower yield.
46.7% With sodium azide; methanesulfonic acid In dichloromethane at 0℃; for 12 h; 2-Methane sulphonic acid (3.1 mL, 47.39 mmol, 10.0 eq) was added to a mixture of 64.1 (1.0 g, 4.74 mmol, 1.0 eq) in CH2Cl2 (10.0 mL) at 0° C. Sodium azide (0.62 g, 9.48 mmol, 2.0 eq) was added slowly in portions. After completion of the addition, mixture was stirred for additional 12 hours. After completion of reaction, aqueous mixture of NaOH (20percent) was added until the mixture was slightly basic. The mixture was extracted with CH2Cl2. Organic layers were combined and solvents evaporated under reduced pressure. The crude material was purified by column chromatography to provide 64.2 (0.5 g, 46.7percent). MS(ES): m/z 226.07 [M+H]+.
45% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃; for 16 h; 5-bromo-indan-1-one (2.35 g, 11.13 mmol) was dissolved in 10 mL of DCM and 10 mL of methanesulfonic acidand cooled to 0°C. Sodium azide (1.45 g, 22.27 mmol) was added thereto, and the mixture was stirred at room temperaturefor 16 hours. The reaction solution was cooled to 0°C, neutralized with NaOH and extracted with EtOAc. The extractwas dried with MgSO4 and purified by column chromatography to obtain the title compound (1.14 g, 45percent).1H-NMR (CDCl3) δ 7.92 (1H, d), 7.48 (1H, d), 7.39 (1H, s), 6.10 (1H, brs), 3.57 (2H, t), 2.99 (2H, t)
44% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃; for 15 h; a) 5-bromofluorenone (1.08 g, 5.12 mmol) was dissolved in 50 mL of methylene chloride and methane sulfonic acid was added slowly at 0°C.(3.32 mL, 51.2 mmol), then slowly adding sodium azide (0.665 g, 10.23 mmol) to the reaction system slowly, slowlyWarm to room temperature and stir for 15 hours. The reaction solution was cooled to 0° C. and 10 mL of 1N sodium hydroxide was slowly added to quench the reaction. DichloromethaneMethane (50 mL*3) was extracted, and the organic layers were combined, sequentially extracted with 100 mL of water and 100 mL of saturated brine, and dried over anhydrous sodium sulfate.The residue was purified by flash column chromatography on silica gel using petroleum ether/ethyl acetate (V/V=5:1) to give compound B0.50g, light yellow solid, yield 44percent
42% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃; 5-bromo-2,3-dihydro-1 H-inden-1 -one (1 K1 ) (9.48mmol, 2g) was dissolved in DCM (35ml) and methane sulfonic acid (95mmol, 9.1 1 g) was added. The reaction mixture was cooled to 0°C before portionwise addition of sodium azide (28.4mmol, 1.85g). Once addition was complete the mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between DCM and NaOH (2M, 50ml). The phases were separated and the aqueous layer was extracted twice more with DCM. The combined organics were washed with water and brine, dried (MgS04) and evaporated to dryness before purification on silica eluting with 75-100percent EtOAc/heptane to give 6-bromo- 3,4-dihydroisoquinolin-1 (2H)-one (1 K2) 919mg (42percent) 1H NMR (400MHz, CDCI3) δ 7.93 (d, 1 H) 7.49 (d, 1 H) 7.40 (s, 1 H) 6.36 (bs, 1 H) 3.58 (t, 2H) 2.99 (t, 2H).
39% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃; 6-Bromo-3,4-dihydroisoquinolin-1(2H)-one (1a)
A solution of 5-bromo-1-indanone (1.08 g, 5.1 mmol) in (2:1) methylene chloride: methanesulfonic acid (45 mL) at 0° C. was treated slowly with sodium azide (0.5 g, 7.7 mmol), allowed to warm to room temperature, stirred overnight and partitioned between methylene chloride and aqueous sodium hydroxide (50 mL, 1.0 N).
The aqueous layer was extracted with methylene chloride.
The combined organic layers were washed sequentially with water and brine, dried over Na2SO4 and concentrated in vacuo.
The residue was purified by ISCO CombiFlash.(R). chromatography (silica, 10-100percent ethyl acetate in hexanes) to afford the title compound as a white solid, 0.45 g (39percent), mp 137-139° C.; MS (ES) m/z [M+H]+ 226.0.
39% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃; for 3 h; 5-bromo-1-indanone (8a) (1.08 g, 5.1 mmol) was weighed and placed in a 100 mL round bottom flask. Methylene chloride (30 mL), methanesulfonic acid (15 mL) and sodium azide (0.5 g, 7.7 mmol) were added to the reaction flask at 0 ° C and the mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched by adding 1.0 M aqueous sodium hydroxide solution (50 mL) to the reaction solution, and the aqueous phase was extracted with dichloromethane (100 mL x 1). The combined organic phases were washed successively with saturated brine (40 mL x 1) Dried sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 3: 1)6-bromo-3,4-dihydro-2H-isoquinolin-1-one (8b) as a gray solid (0.45 g, yield 39percent).
34.8% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 22℃; for 16.5 h; MeSO3H (118 g, 1220 mmol, 80.0 mL) is added to a mixture of 5-bromoindan-1-one(25.0 g, 118 mmol) in DCM (200 mL) at 0 °C. NaN3 (7.78 g, 118 mmol) is added slowly inportions to this mixture. The mixture is then stirred for an additional 30 minutes. The reaction mixture is stirred at 22 °C for 16 hours. The pH is adjusted to 10 with an aqueous mixture of NaOH (20percent wt). The mixture is extracted with DCM (3x450 mL), the organic extracts are combined, dried over MgSO4, and the solvent is removed under reduced pressureto give the crude material as a yellow oil. The residue is purified by silica gel flash chromatography, eluting with a gradient of 0percent to 50percent EtOAc in PE to give the title compound (19.0 g, 34.8percent) as a yellow solid. ES/MS m/z (79Br/81Br): 225.8/ 227.8 (M+H), ‘H NIVIR (400 MHz, CDC13) 7.91 (d, J8.OHz, 1H), 7.48 (dd, J1.8, 8.3 Hz, 1H), 7.39 (s, 1H), 6.84 (br s, 1H), 3.57 (dt, J=2.8, 6.7 Hz, 2H), 2.98 (t, J=6.5 Hz, 2H).
7% With sodium azide; sulfuric acid In water at 0 - 20℃; for 25 h; A suspension of 5-bromo-l-indanone (15 g, 71 retool) in concentrated sulfuric acid (73 mL) was cooled to 0°C. Sodium azide (6.5 g, 100 mmol) was added portionwise over 1 hour. The reaction was allowed to warm to room temperature and stirred for 24 hours. The mixture was poured onto ice, neutralised with 4N sodium hydroxide and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by dry flash chromatography using 50-100percent ethyl acetate/isohexane to give 6-bromo-3,4dihydroisoquinolin-l(2H)-one (1.1 g, 7percent). δ (500 MHz, CDCl3): 7.92 (1 H, d, J = 8.3 HZ), 7.49 (1 H, dd, J = 1.4, 8.3 Hz), 7.39 (1 H, d, J = 0.9 HZ), 6.46 (1 H, s), 3.57-3.55 (2 H, m), 2.98 (2 H, t, J = 6.6 Hz).
3.59 g
Stage #1: With methanesulfonic acid In dichloromethane at 0℃; for 0.0333333 h; Inert atmosphere
Stage #2: With sodium azide In dichloromethane at 0℃; for 2 h;
To a stirred solution of 5-bromoindan-1-one (4 g, 0.0189 mol) in DCM (30 mL) was added methanesulfonic acid (20 mL) and stirred for 2 min at 0° C. under nitrogen atmosphere.
Then sodium azide (2.46 g, 0.0379 mol) was added portionwise and stirred at the same temperature for 2 h.
The reaction was monitored by TLC and LCMS.
After completion of reaction, the mixture was quenched with 20percent NaOH solution and extracted with DCM (2*100 mL).
The combined organic layer was washed with water (2*50 mL) and brine (50 mL).
The organic layer dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product, which was purified by chromatography using eluent 40percent EtOAc in hexane to obtain 6-bromo-3,4-dihydro-2H-isoquinolin-1-one (3.59 g) as an off-white solid.

Reference: [1] Patent: US2010/4231, 2010, A1, . Location in patent: Page/Page column 67-68
[2] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 9, p. 2670 - 2674
[3] Patent: US2016/251376, 2016, A1, . Location in patent: Paragraph 0852; 0853; 0854
[4] Patent: EP3239143, 2017, A2, . Location in patent: Paragraph 0088
[5] Patent: CN107879975, 2018, A, . Location in patent: Paragraph 0132; 0134
[6] Patent: WO2011/51490, 2011, A2, . Location in patent: Page/Page column 22
[7] Patent: US2009/69300, 2009, A1, . Location in patent: Page/Page column 14
[8] Patent: CN106565674, 2017, A, . Location in patent: Paragraph 0283; 0284; 0285; 0286; 0287
[9] Patent: WO2018/160406, 2018, A1, . Location in patent: Page/Page column 10
[10] Patent: WO2006/21805, 2006, A1, . Location in patent: Page/Page column 75
[11] Patent: WO2009/98144, 2009, A1, . Location in patent: Page/Page column 75
[12] Patent: WO2004/65351, 2004, A1, . Location in patent: Page 110
[13] Patent: US2010/222325, 2010, A1, . Location in patent: Page/Page column 98; 107
[14] Patent: EP1724263, 2006, A1, . Location in patent: Page/Page column 40
[15] Journal of Medicinal Chemistry, 2012, vol. 55, # 5, p. 2452 - 2468
[16] Patent: US2018/51013, 2018, A1, . Location in patent: Paragraph 0597; 0598; 0629; 0630
  • 42
  • [ 34598-49-7 ]
  • [ 147497-32-3 ]
  • [ 3279-90-1 ]
YieldReaction ConditionsOperation in experiment
60%
Stage #1: With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃;
Stage #2: With sodium hydroxide In dichloromethane; water at 0℃;
6-Bromo-3,4-dihvdroisoquinolin-l(2H)-one (1A):NaN3 (6.2 g, 94.78 mmol) was added to a solution of 5-bromo-l-indanone (10 g, 47.39 mmol) in 40 mL mixture of methane sulphonic acid and dichloromethane (1 : 1) in portion wise at 0 °C-5 °C. The resulting mixture was stirred for 8 h at room temperature. The reaction mixture was cooled to 0 °C in ice bath, neutralized with 5 percent aq. NaOH solution, and the aqueous layer with extracted with ethyl acetate (2x100 mL). The combined organic layer was washed with water and brine solution, dried over sodium sulphate, filtered and concentrated under vacuum. The residue was purified by silica gel flash column chromatography by eluting with 30 percent ethyl acetate in hexane to afford title compound (6.4 g, 60percent) as solid. 1H NMR (400 MHz, CDC13): δ 7.95 (d, J = 8.4 Hz, 1H), 7.5 (d, J = 8.4 Hz, 1H), 7.4 (s, 1H), 6.1 (bs, 1H), 3.6 (t, J = 6.8 Hz, 2H), 3.0 (t, J = 6.4 Hz, 2H).
60% With sodium azide; methanesulfonic acid In dichloromethane at 0 - 20℃; for 8 h; 2-(i -Oxo-6-(4-(3-(3-(trilluoromethyl)phenyl)ureido) phenyl)-3,4-dihydroisoquinolin-2(i H)-yl)acetic acid6-Hromo-3,4-dihydroisoquinolin-i (2H)-one (iA)Procedures:10443] NaN3 (6.2 g, 94.78 mmol) was added to a solution of5-bromo-i-indanone(iO g, 47.39 mmol) in 40 mL of mixture of methane sulphonic acid and dichloromethane (i : i) in portion wise at 00 C.-5° C. The resulting mixture was stirred for 8 h at room temperature. The reaction mixture was cooled to0°C. in ice bath, neutralized with 5percent aq. NaOH, and aqueous layer was extracted with ethyl acetate (2x1 00 mE). The combined organic layer was washed with water and brine solution, dried over Na2SO4 and filtered. The filtrate was concentrated under vacuum and purified by silica gel flash column chromatography using 30percent ethyl acetate in hexane to afford title compound (6.4 g, 60percent) as solid. ö ‘H NMR (400 MHz, CDC13): ö 7.95 (d, J=8.4 Hz, 1H), 7.5 (d, J=8.4 Hz, 1H), 7.4 (s, 1H), 6.1 (bs, 1H), 3.6 (t, J=6.8 Hz, 2
25% With sodium azide; methanesulfonic acid In chloroform at 0 - 10℃; for 2.5 h; Heating / reflux 5-Bromoindan-1-one (44 g, 209 mmol) was dissolved in CHCl3 (750 mL) with vigorous stirring and cooled to 0° C. Methanesulfonic acid (135 mL, 2090 mmol) was added dropwise. Sodium azide (40.7 g, 625 mmol) was added in portions over 30 min such that the internal temperature did not exceed 10° C. The reaction mixture was heated to reflux temperature and stirred for 2 h. The reaction mixture was cooled to room temperature and poured onto ice (1 kg) with manual stirring. The mixture was neutralized with NH4OH. The layers were separated. The organic solution was dried over MgSO4, filtered and concentrated in vacuo. Column chromatography (EtOAc) provided, after removal of solvent in vacuo: (1) 6-bromo-2H-1,2,3,4-quinol-1-one (10.7 g, 25percent yield): 1H NMR (CDCl3, 300 MHz): 8.11 (br s, 1H), 7.32 (d, 1H, J=1), 7.29 (dd, 1H, J=8, 1), 6.23 (br s, 1H), 6.25 (br s, 1H), 2.98 (t, 2H, J=7), 2.65 (t, 2H, J=7); MS (APCI+): 267, 269 (C11H12BrN2O, M++H+CH3CN) and (2) 6-bromo-1H-1,2,3,4-tetrahydroisoquinolone (21.5 g, 46percent yield): 1H NMR (CDCl3, 300 MHz): 7.95 (d, 1H, J=8), 7.51 (dd, 1H, J=8, 1), 7.21 (t, 1H, J=1), 6.25 (br s, 1H), 3.59 (t, 2H, J=7), 3.01 (t, 2H, J=7); MS (APCI+): 267, 269 (C11H12BrN2O, M++H+CH3CN).
Reference: [1] Patent: WO2012/162129, 2012, A1, . Location in patent: Page/Page column 35
[2] Patent: US2015/307445, 2015, A1, . Location in patent: Paragraph 0441; 0442; 0443
[3] Patent: US2006/63799, 2006, A1, . Location in patent: Page/Page column 9
  • 43
  • [ 75-75-2 ]
  • [ 34598-49-7 ]
  • [ 147497-32-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2018, vol. 61, # 19, p. 8917 - 8933
  • 44
  • [ 34598-49-7 ]
  • [ 724422-42-8 ]
Reference: [1] Patent: US2016/251376, 2016, A1,
[2] Patent: US2018/51013, 2018, A1,
  • 45
  • [ 34598-49-7 ]
  • [ 1082041-78-8 ]
Reference: [1] Patent: WO2018/160406, 2018, A1,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 34598-49-7 ]

Aryls

Chemical Structure| 32281-97-3

[ 32281-97-3 ]

7-Bromo-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.95

Chemical Structure| 66361-67-9

[ 66361-67-9 ]

6-Bromo-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.95

Chemical Structure| 2001-29-8

[ 2001-29-8 ]

1-(4-Bromophenyl)-2-phenylethanone

Similarity: 0.95

Chemical Structure| 1273655-83-6

[ 1273655-83-6 ]

5-Bromo-6-methyl-2,3-dihydro-1H-inden-1-one

Similarity: 0.93

Chemical Structure| 30098-36-3

[ 30098-36-3 ]

7-Bromo-5,8-dimethyl-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.93

Bromides

Chemical Structure| 32281-97-3

[ 32281-97-3 ]

7-Bromo-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.95

Chemical Structure| 66361-67-9

[ 66361-67-9 ]

6-Bromo-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.95

Chemical Structure| 87779-78-0

[ 87779-78-0 ]

3-Bromo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one

Similarity: 0.95

Chemical Structure| 2001-29-8

[ 2001-29-8 ]

1-(4-Bromophenyl)-2-phenylethanone

Similarity: 0.95

Chemical Structure| 1273655-83-6

[ 1273655-83-6 ]

5-Bromo-6-methyl-2,3-dihydro-1H-inden-1-one

Similarity: 0.93

Ketones

Chemical Structure| 32281-97-3

[ 32281-97-3 ]

7-Bromo-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.95

Chemical Structure| 66361-67-9

[ 66361-67-9 ]

6-Bromo-3,4-dihydronaphthalen-1(2H)-one

Similarity: 0.95

Chemical Structure| 87779-78-0

[ 87779-78-0 ]

3-Bromo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one

Similarity: 0.95

Chemical Structure| 2001-29-8

[ 2001-29-8 ]

1-(4-Bromophenyl)-2-phenylethanone

Similarity: 0.95

Chemical Structure| 1273655-83-6

[ 1273655-83-6 ]

5-Bromo-6-methyl-2,3-dihydro-1H-inden-1-one

Similarity: 0.93