[ CAS No. 201940-08-1 ] {[proInfo.proName]}

Name: 201940-08-1|tert-Butyl 5-bromoisoindoline-2-carboxylate|95%
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Product Details of [ 201940-08-1 ]

CAS No. :	201940-08-1	MDL No. :	MFCD09953049
Formula :	C₁₃H₁₆BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GOKHEUCWNVPUSC-UHFFFAOYSA-N
M.W :	298.18	Pubchem ID :	16102683
Synonyms :

Calculated chemistry of [ 201940-08-1 ]

Physicochemical Properties

Num. heavy atoms :	17
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.46
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	74.52
TPSA :	29.54 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.08 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.29
Log Po/w (XLOGP3) :	2.87
Log Po/w (WLOGP) :	3.02
Log Po/w (MLOGP) :	2.92
Log Po/w (SILICOS-IT) :	2.85
Consensus Log Po/w :	2.99

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.56
Solubility :	0.0821 mg/ml ; 0.000275 mol/l
Class :	Soluble
Log S (Ali) :	-3.15
Solubility :	0.211 mg/ml ; 0.000708 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.03
Solubility :	0.0281 mg/ml ; 0.0000942 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.15

Safety of [ 201940-08-1 ]

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

Application In Synthesis of [ 201940-08-1 ]

* 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 [ 201940-08-1 ]
Downstream synthetic route of [ 201940-08-1 ]

[ 201940-08-1 ] Synthesis Path-Upstream 1~9

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[ 201940-08-1 ]
[ 226070-47-9 ]

Reference： [1] Journal of the American Chemical Society, 2016, vol. 138, # 41, p. 13493 - 13496
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 7, p. 1968 - 1972[3] Angew. Chem., 2018, vol. 130, p. 1986 - 1990,5

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[ 201940-08-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate In tetrahydrofuran at 20℃; for 2 h;	To a solution of 4b (6 g, 30 mmol) in THF (100 mE) was added saturated Na2CO3 solution (25 mE), followed by 13oc20 (33 g, 151 mmol). The mixture was stirred at room temperature for 2 hours and evaporated under reduced pressure. The residue was extracted with ethyl acetate (50 mEx3). The combined organic phase was washed with brine, dried over anhydrous Na2504 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA1O:1, v: v) to provide 4c (9 g, ca. 100percent yield). EC-MS: 298 [M+1].
85%	With sodium carbonate In dichloromethane; water for 4 h; Cooling with ice	5-Bromoisoindoline (10.36 g, 52.3 mmol) was dissolved in 80 mL dichloromethane, and cooled in an ice bath. Boc anhydride (22.8 g, 104.6 mmol) was added dropwise followed by the addition of sodium carbonate (16.6 g, 156.9 mmol) and water (150 mL), and stirred in an ice bath for 4 hours. The organic phase was separated, washed with brine, and concentrated, and then the residue was purified by silica gel column chromatography to give the product 5-bromo-2-tert-butoxycarbonylisoindoline (13.3 g). Yield: 85 percent. MS m/z [ESI]: 298.0[M+1]. ¹H-NMR (400 MHz, CDCl₃): δ= 7.37 (2H, m) , 7.11 (1H, m), 4.62 (4H, m), 1.51 (9H, s).
83.4%	With dmap In N,N-dimethyl-formamide at 25℃; for 10 h;	To a solution of 5-bromoisoindoline (3.98 g, 20.2 mmol) in DMF (20 ml) was added DMAP (40.0 mg) and BOC2O (8.81 g, 40.4 mmol). The mixture was stirred at 25°C for 10 h. After LC-MS showed the reaction was completed. The reaction mixture was concentrated to give the crude product, which was washed with pe to give the title compound(5.00 g, 83.4percent). ‘HNMR(400 MHz, CDC13) ö7.39-7.43 (2H,m) 7.09-7.18(1 H, m) 4.61- 4.68(4 H, m) 1.53(9 H, s).

64%	Stage #1: With triethylamine In dichloromethane at 20℃; for 2.5 h; Cooling with ice Stage #2: With N,N-dimethyl-ethanamine In dichloromethane at 20℃; for 1 h; Cooling with ice	Example 7 [1-(pyridin-4-yl)piperidin-4-yl]methyl 2-[amino(imino)methyl]isoindoline-5-carboxylate ditrifluoroacetate; step 1 Synthesis of tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate; To a solution (45 mL) of 5-bromoisoindoline (1.78 g, 9.00 mmol) in dichloromethane were added triethylamine (1.25 mL, 9.00 mmol) and di-tert-butyl dicarbonate (1.96 g, 9.00 mmol) under ice-cooling, and the mixture was stirred at room temperature for 2.5 hr. N,N-Dimethylethylamine (0.988 mL, 9.00 mmol) was added under ice-cooling, the mixture was stirred at room temperature for 1 hr, and 1 N hydrochloric acid was added to the reaction mixture. The mixture was extracted with dichloromethane, and the extract was washed with 1 N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane:ethyl acetate 100:0 - 92:8) to give the title compound. yield (1.72 g, 5.76 mmol, 64percent) MS (ESI, m/z) 284 [(M-Me)+H]⁺ ¹H-NMR (CDCl₃)δ1.51 (s, 9H), 4.59-4.67 (m, 4H), 7.08-7.15 (m, 1H), 7.36-7.42 (m, 2H).
61%	With sodium hydrogencarbonate In tetrahydrofuran at 20℃;	To a solution of 5-bromoisoindoline (1.3 g, 6.6 mmol) in THF (30 mL) were added NaHCC (1.66 g, 19.8 mmol) and (Boc)₂0 (4.3 g, 19.8 mmol). The reaction was stirred at rt overnight, then concentrated in vacuo. The residue was partitioned between H₂0 (40 mL) and DCM (40 mL), and the aqueous phase was extracted with DCM (60 mL x 2). The combined organic phases were dried over anhydrous a₂S0₄, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) = 5/1) to give the title compound as a pale yellow solid (1.2 g, 61percent). MS (ESI, pos. ion) m/z: 244.0 [M-56+l]⁺; NMR (400 MHz, CDC1₃) δ (ppm): 7.35-7.41 (m, 2H), 7.07-7.14 (m, 1H), 4.58-4.66 (m, 4H), 1.51 (s, 9H).
61%	With sodium hydrogencarbonate In tetrahydrofuran at 20℃;	5-bromoisoindoline (1.3 g, 6.6 mmol)Was dissolved in tetrahydrofuran (30 mL)To this was added sodium bicarbonate (1.66 g, 19.8 mmol) andBoc anhydride (4.3 g, 19.8 mmol).The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure.The residue was partitioned between dichloromethane (40 mL) and water (40 mL) and the separated aqueous phase was extracted with dichloromethane (60 mL x 2).There are mergersThe organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5/1) to give the title compound as a pale yellow solid (1.2 g, 61percent).
53%	With dmap In tetrahydrofuran at 20℃; for 3 h;	To a solution of 5-bromo-2,3-dihydro-lH-isoindole (8.75 g; 1.0 equiv) in THF (126 mL) are added di-fert-butyldicarbonate (10.8 g; 1.12 equiv) and 4-dimethylaminopyridine (5.4 g; 1.0 equiv) and the reaction is stirred at room temperature for 3 h. The reaction is quenched with saturated sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic extracts are dried (MgSO₄), filtered, and concentrated to afford crude product, which is purified by silica gel chromatography to yield 7.0 g 5-bromo-l,3-dihydro- isoindole-2-carboxylic acid tert-butyl ester (23.49 mmol; 53percent yield over two steps). ¹H NMR (400 MHz, CD₃OD): δ 7.39 (dd, J= 4.0, 16.0 Hz, 1 H), 7.26 (s, 1 H), 7.12 (dd, J = 20.0, 4.0 Hz), 4.67 (s, 1 H), 4.62 (s, 2 H), 4.59 (s, 1 H), 1.51 (s, 9 H).

Reference： [1] Patent: US2017/275301, 2017, A1, . Location in patent: Paragraph 0226; 0228
[2] Patent: EP3257857, 2017, A1, . Location in patent: Paragraph 0102; 0104
[3] Journal of Organic Chemistry, 2012, vol. 77, # 24, p. 11296 - 11301
[4] Patent: WO2015/54317, 2015, A1, . Location in patent: Paragraph 0272; 0273
[5] Patent: EP2311810, 2011, A1, . Location in patent: Page/Page column 24
[6] Patent: WO2014/89324, 2014, A1, . Location in patent: Paragraph 0236
[7] Patent: CN104016979, 2017, B, . Location in patent: Paragraph 0602; 0603; 0604; 0605
[8] Patent: WO2008/76954, 2008, A2, . Location in patent: Page/Page column 54
[9] Journal of Medicinal Chemistry, 2007, vol. 50, # 2, p. 199 - 210
[10] Patent: US2008/171754, 2008, A1, . Location in patent: Page/Page column 103
[11] Patent: WO2008/44029, 2008, A1, . Location in patent: Page/Page column 235
[12] Patent: WO2008/44041, 2008, A1, . Location in patent: Page/Page column 257
[13] Patent: WO2008/44045, 2008, A1, . Location in patent: Page/Page column 310
[14] Patent: WO2008/44054, 2008, A2, . Location in patent: Page/Page column 154
[15] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 14, p. 4159 - 4162
[16] Patent: US2010/152184, 2010, A1, . Location in patent: Page/Page column 97
[17] Journal of Medicinal Chemistry, 2010, vol. 53, # 16, p. 5956 - 5969
[18] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 16, p. 4909 - 4912

3
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Yield	Reaction Conditions	Operation in experiment
88%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1 h;	A solution of 5-bromoisoindoline, HC1 (255 mg, 1.00 mmol) in DCM (5 mL) was treated with DIEA (0.570 mL, 3.26 mmol) and (Boc)20 (0.290 mL, 1.25 mmol). The mixture was stirred at rt for 1 h. The reaction was quenched with brine and extracted withDCM (2x). The combined organic extracts were dried over MgSO4, filtered, and concentrated to afford the crude product, which was purified by silica gelchromatography to provide 176A (0.28 g, 88percent yield). MS(ESI) m/z 243.9 (M+H-tBu)t ‘H NMR (500MHz, CDC13)ö 7.45-7.35 (m, 2H), 7.17-7.08 (m, 1H), 4.68-4.60(m, 4H), 1.52 (s, 9H).

Reference： [1] Patent: WO2017/40449, 2017, A1, . Location in patent: Paragraph 00449

4
[ 6941-75-9 ]
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[ 201940-08-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	at 10 - 35℃; for 15 h;	Boc₂O (2.58 g, 11.82 mmol) was added to a mixture of 5-bromoisoindoline-1,3-dione (2.23 g, 11.26 mmol) in THF (35 mL) at room temperature, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 0→14percent ethyl acetate/hexane) to give tert-butyl 5-bromoisoindoline-2-carboxylate (2.35 g, 7.88 mmol, 70.0percent) as a white solid. ¹H NMR (300 MHz, CDCl₃):δ 1.51(9H,s), 4.58-4.68(4H,m), 7.07-7.17(1H,m), 7.35-7.44(2H,m).
57.6%	Stage #1: With borane-THF In tetrahydrofuran at 0℃; for 36.5 h; Reflux Stage #2: for 4 h; Reflux Stage #3: With dmap In tetrahydrofuran at 20℃; for 4 h;	General procedure: Toa solution of 4a (10.0 g, 35.3 mmol)in MeOH (200 mL) was added 8M KOH solution (20 mL) and then heated to reflux.After 36 h, the reaction mixture was concentrated under reduced pressure.The mixture was diluted with H₂O (100 mL), extracted with EA (75 mL×2), dried over Na₂SO₄ and concentrated under reducedpressure. The residue was dissolved in THF (100 mL). Di-tert-butyldicarbonate (9.0 g, 41.2 mmol) and DMAP (0.5 g, 4.0 mmol) was added and thenthe reaction mixture was stirred at room temperature for 4 h. Afterconcentration, the residue was purified by silica gel column chromatography(PET/EA = 15:1, v/v) to affordcompound 5a as colorless oil (8.3 g,75.5percent).

Reference： [1] Patent: EP3192791, 2017, A1, . Location in patent: Paragraph 0599
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 18, p. 3050 - 3056

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Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 2, p. 199 - 210
[2] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 16, p. 4909 - 4912
[3] Journal of Organic Chemistry, 2012, vol. 77, # 24, p. 11296 - 11301
[4] Patent: WO2014/89324, 2014, A1,
[5] Patent: WO2015/54317, 2015, A1,
[6] Patent: CN104016979, 2017, B,
[7] Patent: US2017/275301, 2017, A1,
[8] Patent: EP3257857, 2017, A1,

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Reference： [1] Patent: US2010/119479, 2010, A1,

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[ 86-90-8 ]
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Reference： [1] Patent: WO2014/89324, 2014, A1,
[2] Patent: CN104016979, 2017, B,

8
[ 201940-08-1 ]
[ 73183-34-3 ]
[ 905273-91-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In dimethyl sulfoxide at 90℃; for 12 h; Inert atmosphere	To a suspension of tert-butyl 5-bromo-2-(tert-butoxycarbonyl)isoindoline (1.2 g, 4 mmol) and bis(pinacolato)diboron (2 g, 8 mmol) in DMSO (20 mL) was added AcOK (1.6 g, 16 mmol), followed by Pd(dppf)Cl₂-CH₂Cl₂ (327 mg, 0.4 mmol) under N₂ atmosphere. The reaction was heated at 90 °C for 12 h, then cooled to rt and poured into EtOAc/H₂0 (300 mL/100 mL). The separatedorganic phase was washed with brine (100 mL), dried over anhydrous Na₂S0₄, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) =20/1) to give the title compound as yellow oil (1 g, 73percent). MS (ESI, pos. ion) m/z: 290.2 [M-56+l ; NMR (400 MHz, CDC1₃) δ (ppm): 7.68-7.74 (m, 2H), 7.23-7.30 (m, 1H), 4.64-4.70 (m, 4H), 1.53 (s, 9H), 1.36 (s, 12H).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In dimethyl sulfoxide at 90℃; for 12 h; Inert atmosphere	Under nitrogen protection,A solution of 5-bromo-2- (tert-butoxycarbonyl) isoindoline (1.2 g, 4 mmol)And boronic acid pinacol ester (2 g, 8 mmol)Was dissolved in dimethylsulfoxide (20 mL)To this was added potassium acetate (1.6 g, 16 mmol) andPd (dppf) Cl2CH2Cl2 (327 mg, 0.4 mmol).The reaction solution was heated and stirred at 90 ° C for 12 hours,Cool to room temperature and pour into acetic acidEthyl acetate / water (300 mL / 100 mL), the separated organic phase was washed with brine (100 mL), dried over anhydrous sodium sulfate,Filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 20/1)The title compound was obtained as a yellow oil (1 g, 73percent).
72%	With potassium acetate In N,N-dimethyl-formamide at 85℃; for 4 h;	Step 2: tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate A solution of tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.80 mmol), bis(pinacolato)diboron (0.96 mmol) and potassium acetate (2.5 mmol) in DMF (4 mL) was degassed. To this solution was added PdCl₂dppf (1:1 complex with DCM, 0.04 mmol). The reaction mixture was heated at 85° C. for 4 hr and then allowed to cool to rt and diluted with EtOAc. The solution was washed with water and brine, dried over Na₂SO₄, filtered and concentrated. The residue was purified by column chromatography (10-30percent EtOAc in hexane) to give tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate (0.57 mmol, 72percent) as a white solid. LCMS: (FA) ES+346.

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 2, p. 199 - 210
[2] Patent: WO2014/89324, 2014, A1, . Location in patent: Paragraph 0237
[3] Patent: CN104016979, 2017, B, . Location in patent: Paragraph 0606; 0607; 0608; 0609
[4] Patent: US2008/171754, 2008, A1, . Location in patent: Page/Page column 103
[5] Patent: WO2010/10186, 2010, A1, . Location in patent: Page/Page column 58
[6] Patent: WO2010/145202, 2010, A1, . Location in patent: Page/Page column 59
[7] Patent: WO2015/112441, 2015, A1, . Location in patent: Page/Page column 56
[8] Patent: US2016/333021, 2016, A1, . Location in patent: Paragraph 0345

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Reference： [1] Journal of Organic Chemistry, 2012, vol. 77, # 24, p. 11296 - 11301

[ 201940-08-1 ] Synthesis Path-Downstream 1~88

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[ 127168-84-7 ]
[ 201940-08-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate; In tetrahydrofuran; at 20℃; for 2h;	To a solution of 4b (6 g, 30 mmol) in THF (100 mE) was added saturated Na2CO3 solution (25 mE), followed by 13oc20 (33 g, 151 mmol). The mixture was stirred at room temperature for 2 hours and evaporated under reduced pressure. The residue was extracted with ethyl acetate (50 mEx3). The combined organic phase was washed with brine, dried over anhydrous Na2504 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA1O:1, v: v) to provide 4c (9 g, ca. 100% yield). EC-MS: 298 [M+1].
85%	With sodium carbonate; In dichloromethane; water; for 4h;Cooling with ice;	5-Bromoisoindoline (10.36 g, 52.3 mmol) was dissolved in 80 mL dichloromethane, and cooled in an ice bath. Boc anhydride (22.8 g, 104.6 mmol) was added dropwise followed by the addition of sodium carbonate (16.6 g, 156.9 mmol) and water (150 mL), and stirred in an ice bath for 4 hours. The organic phase was separated, washed with brine, and concentrated, and then the residue was purified by silica gel column chromatography to give the product 5-bromo-2-tert-butoxycarbonylisoindoline (13.3 g). Yield: 85 %. MS m/z [ESI]: 298.0[M+1]. 1H-NMR (400 MHz, CDCl3): delta= 7.37 (2H, m) , 7.11 (1H, m), 4.62 (4H, m), 1.51 (9H, s).
83.4%	With dmap; In N,N-dimethyl-formamide; at 25℃; for 10h;	To a solution of 5-bromoisoindoline (3.98 g, 20.2 mmol) in DMF (20 ml) was added DMAP (40.0 mg) and BOC2O (8.81 g, 40.4 mmol). The mixture was stirred at 25C for 10 h. After LC-MS showed the reaction was completed. The reaction mixture was concentrated to give the crude product, which was washed with pe to give the title compound(5.00 g, 83.4%). ?HNMR(400 MHz, CDC13) oe7.39-7.43 (2H,m) 7.09-7.18(1 H, m) 4.61- 4.68(4 H, m) 1.53(9 H, s).

82.1%	With dmap; In tetrahydrofuran; at 20℃; for 4h;	Intermediate 7 (5.0 g, 25.4 mmol) was dissolved in tetrahydrofuran (100 mL).Add DMAP (0.5 g, 4.0 mmol) in turn,Boc anhydride (10.0 g, 44.2 mmol), stirred at room temperature for 4 h, concentrated and then purified.6.2 g (82.1%) of an oil was obtained.
64%		Example 7 [1-(pyridin-4-yl)piperidin-4-yl]methyl 2-[amino(imino)methyl]isoindoline-5-carboxylate ditrifluoroacetate; step 1 Synthesis of tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate; To a solution (45 mL) of 5-bromoisoindoline (1.78 g, 9.00 mmol) in dichloromethane were added triethylamine (1.25 mL, 9.00 mmol) and di-tert-butyl dicarbonate (1.96 g, 9.00 mmol) under ice-cooling, and the mixture was stirred at room temperature for 2.5 hr. N,N-Dimethylethylamine (0.988 mL, 9.00 mmol) was added under ice-cooling, the mixture was stirred at room temperature for 1 hr, and 1 N hydrochloric acid was added to the reaction mixture. The mixture was extracted with dichloromethane, and the extract was washed with 1 N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane:ethyl acetate 100:0 - 92:8) to give the title compound. yield (1.72 g, 5.76 mmol, 64%) MS (ESI, m/z) 284 [(M-Me)+H]+ 1H-NMR (CDCl3)delta1.51 (s, 9H), 4.59-4.67 (m, 4H), 7.08-7.15 (m, 1H), 7.36-7.42 (m, 2H).
61%	With sodium hydrogencarbonate; In tetrahydrofuran; at 20℃;	To a solution of 5-bromoisoindoline (1.3 g, 6.6 mmol) in THF (30 mL) were added NaHCC (1.66 g, 19.8 mmol) and (Boc)20 (4.3 g, 19.8 mmol). The reaction was stirred at rt overnight, then concentrated in vacuo. The residue was partitioned between H20 (40 mL) and DCM (40 mL), and the aqueous phase was extracted with DCM (60 mL x 2). The combined organic phases were dried over anhydrous a2S04, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) = 5/1) to give the title compound as a pale yellow solid (1.2 g, 61%). MS (ESI, pos. ion) m/z: 244.0 [M-56+l]+; NMR (400 MHz, CDC13) delta (ppm): 7.35-7.41 (m, 2H), 7.07-7.14 (m, 1H), 4.58-4.66 (m, 4H), 1.51 (s, 9H).
61%	With sodium hydrogencarbonate; In tetrahydrofuran; at 20℃;	5-bromoisoindoline (1.3 g, 6.6 mmol)Was dissolved in tetrahydrofuran (30 mL)To this was added sodium bicarbonate (1.66 g, 19.8 mmol) andBoc anhydride (4.3 g, 19.8 mmol).The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure.The residue was partitioned between dichloromethane (40 mL) and water (40 mL) and the separated aqueous phase was extracted with dichloromethane (60 mL x 2).There are mergersThe organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5/1) to give the title compound as a pale yellow solid (1.2 g, 61%).
59.8%	With dmap; In N,N-dimethyl-formamide; at 20℃; for 12h;	At 20 C., to a system of WX042-2 (5.00 g, 22.12 mmol) and Boc2O (1.21 g, 5.56 mmol) in N, N-dimethylformamide (10.00 mL) was added DMAP (61.70 mg, 505.00 mumol), and the system was stirred at 20 C. for 12 hours. After the reaction was complete, the system was extracted with ethyl acetate (15 mL×3). The organic layer was washed separately with water (10 mL×3) and brine (10 mL×2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether:ethyl acetate=5:1) to afford Compound WX042-3 (900.00 mg, 59.80% yield), white solid. 1H NMR (400 MHz, CDCl3) delta 7.42-7.36 (m, 2H), 7.17-7.08 (m, 1H), 4.67-4.59 (m, 4H), 1.51 (s, 9H).
53%	With dmap; In tetrahydrofuran; at 20℃; for 3h;	To a solution of 5-bromo-2,3-dihydro-lH-isoindole (8.75 g; 1.0 equiv) in THF (126 mL) are added di-fert-butyldicarbonate (10.8 g; 1.12 equiv) and 4-dimethylaminopyridine (5.4 g; 1.0 equiv) and the reaction is stirred at room temperature for 3 h. The reaction is quenched with saturated sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic extracts are dried (MgSO4), filtered, and concentrated to afford crude product, which is purified by silica gel chromatography to yield 7.0 g 5-bromo-l,3-dihydro- isoindole-2-carboxylic acid tert-butyl ester (23.49 mmol; 53% yield over two steps). 1H NMR (400 MHz, CD3OD): delta 7.39 (dd, J= 4.0, 16.0 Hz, 1 H), 7.26 (s, 1 H), 7.12 (dd, J = 20.0, 4.0 Hz), 4.67 (s, 1 H), 4.62 (s, 2 H), 4.59 (s, 1 H), 1.51 (s, 9 H).
	With potassium carbonate; In tetrahydrofuran; water; at 20℃;	Step 1: tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate To a solution of 5-bromo-1H-isoindole-1,3(2H)-dione (4 mmol) in THF (10 mL) was added borane-dimethyl sulfide complex (2M in THF, 14 mL) at 0 C. The reaction mixture was allowed to stir at reflux overnight and was then cooled to 0 C. The reaction mixture was quenched by the slow addition of MeOH (10 mL) and then 2N HCl (10 mL). The reaction mixture was allowed to stir at reflux for 3 hr and then concentrated. Water (10 mL) was added to the residue. Remaining starting material was removed by extraction with DCM. To the aqueous solution was added 4N NaOH until pH>9. The solution was extracted with DCM. The organic solutions from this basic extraction were combined, dried over Na2SO4, filtered and concentrated to give 5-bromoisoindoline, which was dissolved in THF (20 mL). To this solution was added potassium carbonate (8 mmol) in water (1 mL), and BOC2O. The reaction mixture was allowed to stir at rt over the weekend. The reaction mixture was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (2.5 mmol, 60%).
	dmap; In N,N-dimethyl-formamide; at 20℃;	A mixture of 5-bromo-2,3-dihydro-1H-isoindole (1.26 g; 6.4 mmol), di-tert-butyl dicarbonate (1.53 g; 1.1 equiv.) and 4-dimethylaminopyridine (catalytic amount) in DMF (20 ml) was stirred at room temperature overnight then evaporated. The residue was partitioned between EtOAc and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography using a Biotage SP4 (4OS, 40 ml/min) eluting with 0% to 5% MeOH / DCM gave 695 mg of 5-bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a brown gum. 1HNMR (DMSO-d6) 7.55 (1H, d), 7.48 (1H1 d), 7.30 (1H, dd), 4.63-4.51 (4H, m), 1.46 (9H, s).
	dmap; In N,N-dimethyl-formamide; at 20℃;	A mixture of 5-bromo-2,3-dihydro-1 H-isoindole (1.26 g; 6.4 mmol), di-tert-butyl dicarbonate (1.53 g; 1.1 equiv.) and 4-dimethylaminopyridine (catalytic amount) in DMF (20 ml) was stirred at room temperature overnight then evaporated. The residue was partitioned between EtOAc and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography using a Biotage SP4 (4OS, 40 ml/min) eluting with 0% to 5% MeOH / DCM gave 695 mg of 5-bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a brown gum. 1HNMR (DMSO-d6) 7.55 (1H, d), 7.48 (1 H, d), 7.30 (1 H, dd). 4.63-4.51 (4H, m), 1.46 (9H, s).
	dmap; In N,N-dimethyl-formamide; at 20℃;	A mixture of 5-bromo-2,3-dihydro-1H-isoindole (1.26 g; 6.4 mmol), di-tert-butyl dicarbonate (1.53 g; 1.1 equiv.) and 4-dimethylaminopyridine (catalytic amount) in DMF (20 ml) was stirred at room temperature overnight then evaporated. The residue was partitioned between EtOAc and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography using a Biotage SP4 (4OS, 40 ml/min) eluting with 0% to 5% MeOH / DCM gave 695 mg of 5-bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a brown gum. 1HNMR (DMSO-d6) 7.55 (1H, d), 7.48 (1H, d), 7.30 (1 H, dd), 4.63-4.51 (4H1 m), 1.46 (9H, s).
	dmap; In N,N-dimethyl-formamide; at 20℃;	A mixture of 5-bromo-2,3-dihydro-1 H-isoindole (1.26 g; 6.4 mmol), di-tert-butyl dicarbonate (1.53 g; 1.1 equiv.) and 4-dimethylaminopyridine (catalytic amount) in DMF (20 ml) was stirred at room temperature overnight then evaporated. The residue was partitioned between EtOAc and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography using a Biotage SP4 (4OS, 40 ml/min) eluting with 0% to 5% MeOH / DCM gave 695 mg of 5-bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a brown gum. 1HNMR (DMSO-d6) 7.55 (1 H, d), 7.48 (1 H, d), 7.30 (1 H, dd), 4.63-4.51 (4H, m), 1.46 (9H, s).
	With dmap; In N,N-dimethyl-formamide; at 20℃;	A mixture of 5-bromo-2,3-dihydro-1H-isoindole (1.26 g; 6.4 mmol), di-tert-butyl dicarbonate (1.53 g; 1.1 equiv.) and 4-dimethylaminopyridine (catalytic amount) in DMF (20 ml) was stirred at room temperature overnight then evaporated. The residue was partitioned between EtOAc and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography using a Biotage SP4 (40S, 40 ml/min) eluting with 0% to 5% MeOH/DCM gave 695 mg of 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a brown gum. 1HNMR (DMSO-d6) 7.55 (1H, d), 7.48 (1H, d), 7.30 (1H, dd), 4.63-4.51 (4H, m), 1.46 (9H, s).

Reference： [1]Patent: US2017/275301,2017,A1 .Location in patent: Paragraph 0226; 0228
[2]Patent: EP3257857,2017,A1 .Location in patent: Paragraph 0102; 0104
[3]Journal of Organic Chemistry,2012,vol. 77,p. 11296 - 11301
[4]Patent: WO2015/54317,2015,A1 .Location in patent: Paragraph 0272; 0273
[5]Patent: CN110294744,2019,A .Location in patent: Paragraph 0163-0165; 0189-0191
[6]Patent: EP2311810,2011,A1 .Location in patent: Page/Page column 24
[7]Patent: WO2014/89324,2014,A1 .Location in patent: Paragraph 0236
[8]Patent: CN104016979,2017,B .Location in patent: Paragraph 0602; 0603; 0604; 0605
[9]Patent: US2019/375744,2019,A1 .Location in patent: Paragraph 0107; 0109
[10]Journal of Medicinal Chemistry,2019,vol. 62,p. 7431 - 7444
[11]Patent: WO2008/76954,2008,A2 .Location in patent: Page/Page column 54
[12]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210
[13]Patent: US2008/171754,2008,A1 .Location in patent: Page/Page column 103
[14]Patent: WO2008/44029,2008,A1 .Location in patent: Page/Page column 235
[15]Patent: WO2008/44041,2008,A1 .Location in patent: Page/Page column 257
[16]Patent: WO2008/44045,2008,A1 .Location in patent: Page/Page column 310
[17]Patent: WO2008/44054,2008,A2 .Location in patent: Page/Page column 154
[18]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4159 - 4162
[19]Patent: US2010/152184,2010,A1 .Location in patent: Page/Page column 97
[20]Journal of Medicinal Chemistry,2010,vol. 53,p. 5956 - 5969
[21]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4909 - 4912

2
[ 201940-08-1 ]
[ 73183-34-3 ]
[ 905273-91-8 ]

Yield	Reaction Conditions	Operation in experiment
99.3%		Tert-butyl-5-bromisoindoline-2-carboxylate (20.0 g, 67.09 mmol) was dissolved in Dioxane (200 ml.) and the solution was purged with Argon gas for 10 min. Bispinacalato diborane (34.07 g, 134.18 mmol), KOAc (26.34 g, 268.36 mmol) and Pd(PPh3)4 (7.75 g, 6.70 mmol) were added and the reaction mixture was stirred at 80C for 12 h. Reaction mixture was diluted with water, extracted with EtOAc (1 Ltr. X 2) twice The combined organic layers were washed with water (500 ml_), brine (300 ml_), dried over sodium sulphate and concentrated under vacuo. Crude compound was purified by Combiflash chromatography using 40 g Column and 10% EtOAc in n-Hexane to afford title compound as a White solid 23.0 g (99.30 %). Rf = 0.50 (10% EtOAc in n-Hexane); 1 H NMR (300 MHz, CDCI3): d 7.72-7.65 (m, 2H), 7.31 -7.20 (m, 1 H), 4.70-4.60 (m, 4H), 1 .40 (s, 9 H), 1 .37 (s, 12H).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In dimethyl sulfoxide; at 90℃; for 12h;Inert atmosphere;	To a suspension of tert-butyl 5-bromo-2-(tert-butoxycarbonyl)isoindoline (1.2 g, 4 mmol) and bis(pinacolato)diboron (2 g, 8 mmol) in DMSO (20 mL) was added AcOK (1.6 g, 16 mmol), followed by Pd(dppf)Cl2-CH2Cl2 (327 mg, 0.4 mmol) under N2 atmosphere. The reaction was heated at 90 C for 12 h, then cooled to rt and poured into EtOAc/H20 (300 mL/100 mL). The separatedorganic phase was washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) =20/1) to give the title compound as yellow oil (1 g, 73%). MS (ESI, pos. ion) m/z: 290.2 [M-56+l ; NMR (400 MHz, CDC13) delta (ppm): 7.68-7.74 (m, 2H), 7.23-7.30 (m, 1H), 4.64-4.70 (m, 4H), 1.53 (s, 9H), 1.36 (s, 12H).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 90℃; for 12h;Inert atmosphere;	Under nitrogen protection,A solution of 5-bromo-2- (tert-butoxycarbonyl) isoindoline (1.2 g, 4 mmol)And boronic acid pinacol ester (2 g, 8 mmol)Was dissolved in dimethylsulfoxide (20 mL)To this was added potassium acetate (1.6 g, 16 mmol) andPd (dppf) Cl2CH2Cl2 (327 mg, 0.4 mmol).The reaction solution was heated and stirred at 90 C for 12 hours,Cool to room temperature and pour into acetic acidEthyl acetate / water (300 mL / 100 mL), the separated organic phase was washed with brine (100 mL), dried over anhydrous sodium sulfate,Filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 20/1)The title compound was obtained as a yellow oil (1 g, 73%).

72%	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 85℃; for 4h;	Step 2: tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate A solution of tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.80 mmol), bis(pinacolato)diboron (0.96 mmol) and potassium acetate (2.5 mmol) in DMF (4 mL) was degassed. To this solution was added PdCl2dppf (1:1 complex with DCM, 0.04 mmol). The reaction mixture was heated at 85 C. for 4 hr and then allowed to cool to rt and diluted with EtOAc. The solution was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (10-30% EtOAc in hexane) to give tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate (0.57 mmol, 72%) as a white solid. LCMS: (FA) ES+346.
36%	With tetrakis(triphenylphosphine) palladium(0); potassium acetate; In dimethyl sulfoxide; at 80℃; for 16h;Inert atmosphere;	To a solution of tert-butyl 5-bromoisoindoline-2-carboxylate (1.20 g, 4.02 mmol, CAS201940-08-1), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.12 g, 4.43 mmol) in DMSO (20.0 mL) was added KOAc (1.18 g, 12.0 mmol) and Pd(PPh3)4 (139 mg, 120 umol). The mixture was stirred at 80 C. for 16 hours under N2. On completion, the mixture was diluted with H2O (50 mL), and extracted with EA (3×30 mL). The organic layers were washed with brine (3×30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The mixture was purified by prep-HPLC (reserve phase (0.1% FA)) to give the title compound (500 mg, 36% yield) as yellow solid. 1H NMR (400 MHz, CDCl3) delta 7.75 (s, 1H), 7.32-7.29 (m, 1H), 7.25 (d, J=7.6 Hz, 1H), 4.74-4.66 (m, 4H), 1.54 (s, 9H), 1.37 (s, 12H).
	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 20h;Inert atmosphere;	In a microwave vessel, a solution of 5-bromo-l,3-dihydro-isoindole-2-carboxylic acid tert- butyl ester (1.5 equiv.), di(pinacolato)diborane (2.0 equiv.), potassium acetate (2.0 equiv.) in 1,4-dioxane (2.0 mL) is flushed with nitrogen. [l,l'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 equiv.) was then added and the reaction mixture was flushed again with argon (and heated up to 900C for 20 hours until the reaction is complete on TLC. No purification was carried out.
	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 120℃; for 1h;Microwave irradiation;Product distribution / selectivity;	A flask was charged with 1,1-dimethylethyl 5-bromo-1 ,3-dihydro-2H-isoindole-2- carboxylate (CASNo. 201940-08-1, commercially available from AB chemical, 53.6 mg, 0.180 mmol), potassium acetate (52.9 mg, 0.540 mmol), 4,4,4',4',5,5,5',S'- octamethyl-2,2'-bi-1,3,2-dioxaborolane (45.7 mg, 0.180 mmol) and 1,1'- bis(diphenylphosphino)ferrocenedichloro palladium(ll) (13.16 mg, 0.018 mmol) then filled with DME (2 ml) and the resulting mixture was stirred at 1200C for 60 minutes under microwave irradiation. 2-Bromo-5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}- 1,3,4-thiadiazole (Preparation 11) (60.0 mg, 0.180 mmol) was added along with a saturated NaHCO3 aqueous solution (0.2 ml). The resulting mixture was stirred at 120C for 60 minutes under microwave irradiation then at 1400C for 30 minutes, still under microwave irradiation. The insoluble material was filtered off via a pad of silica gel and rinsed with DCM and AcOEt. The combined organic phases were concentrated in vacuo and the residue dissolved in DCM (5 ml) and trifluoroacetic acid (3 ml, 38.9 mmol). The resulting mixture was stirred at room temperature for 2 hours then concentrated in vacuo. The residue was loaded on a SCX cartridge and eluted with MeOH then with a 2N NH3 solution in MeOH. The combined ammonia fractions were combined and concentrated in vacuo. Purification of the residue by MDAP gave 5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1 ,3,4-thiadiazol-2-yl)-2,3- dihydro-1 H-isoindole trifluoroacetic acid salt (15.1 mg, 17.3 % yield) as a white foam. LCMS: retention time 1.07 min; [M+H]+ = 372.2
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃;	Commercially available tert-butyl 5-bromoisoindoline-2-carboxylate (i.e., Matric Scientific, catalog 74109) (20 g, 0.0671 mol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2- dioxaborolane) (17 g, 0.0671 mol), KAc (8.5 g, 0.087 mol) and PdCfedppf (1.8 g, 0.00221 mol) in 200 mL 1,4-dioxane was heated to 80C overnight. The mixture was cooled, water was added, the mixture was extacted with EA, dried and concentrated. The residue was purified by chromatography on silica gel to afford the title compound. 1HNMR (300MHz,DMSO)5: 1.2-1.3 (s, 12H), 1.4-1.5 (s, 9H), 4.5-4.6 (s, 4H), 7.2-7.3(m,lH), 7.5-7.6 (M,2H); LC-MS: m/z=246 (M+l-100)+.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃;	Reference Example 17 tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindoline-2-carboxylate (0344) tert-butyl 5-bromoisoindoline-2-carboxylate (i.e., Matric Scientific, catalog 74109) (20 g, 0.0671 mol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (17 g, 0.0671 mol), KAc (8.5 g, 0.087 mol) and PdCl2dppf (1.8 g, 0.00221 mol) in 200 mL 1,4-dioxane was heated to 80 C. overnight. The mixture was cooled, water was added, the mixture was extracted with EA, dried and concentrated. The residue was purified by chromatography on silica gel to afford the title compound. 1HNMR (300 MHz, DMSO) delta: 1.2-1.3 (s, 12H), 1.4-1.5 (s, 9H), 4.5-4.6 (s, 4H), 7.2-7.3 (m, 1H), 7.5-7.6 (M, 2H); LC-MS: m/z=246 (M+1-100)+.

Reference： [1]Patent: WO2019/244049,2019,A1 .Location in patent: Paragraph 00180; 00212; 00214
[2]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210
[3]Patent: WO2014/89324,2014,A1 .Location in patent: Paragraph 0237
[4]Patent: CN104016979,2017,B .Location in patent: Paragraph 0606; 0607; 0608; 0609
[5]Patent: US2008/171754,2008,A1 .Location in patent: Page/Page column 103
[6]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 2685; 2686
[7]Patent: WO2010/10186,2010,A1 .Location in patent: Page/Page column 58
[8]Patent: WO2010/145202,2010,A1 .Location in patent: Page/Page column 59
[9]Patent: WO2015/112441,2015,A1 .Location in patent: Page/Page column 56
[10]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0345

3
[ 201940-08-1 ]
[ 368441-44-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethanolamine;palladium diacetate; In methanol; dimethyl sulfoxide;	Example 3-91 a 2,3-Dihydro-1H-isoindole-5-carboxylic acid methyl ester was synthesised according to the following scheme: A mixture of <strong>[201940-08-1]5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester</strong> (200 mg, 0.67 mmol), Pd(OAc)2 (30 mg, 0.2 equiv), DPPP (55 mg, 0.2 equiv), TEA (0.93 mL, 10 equiv) and MeOH:DMSO (1:1, 4 mL) was stirred for 16 h under CO (balloon) at 80 C. LC-MS and TLC (20% EtOAc-Hexane) showed completion of the reaction. The Reaction mixture was concentrated to remove MeOH and diluted with EtOAc (10 mL), and washed with water (2*25 mL). The organic layer was dried (Na2SO4), concentrated and purified by silica gel column chromatography (eluent=20% EtOAc-Hexane), giving pure 1,3-dihydro-isoindole-2,5-dicarboxylic acid 2-tert-butyl ester 5-methyl ester (150 mg, 81%). MS (APCI+): m/z 178.1 (MH+-Boc).

Reference： [1]Patent: US2005/267018,2005,A1

4
[ 201940-08-1 ]
9-cyclopropyl-7-(2,3-dihydro-1H-isoindol-5-yl)-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210

5
[ 201940-08-1 ]
9-cyclopropyl-7-(2,3-dihydro-1H-isoindol-5-yl)-6-fiuoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210

6
[ 201940-08-1 ]
9-cyclopropyl-6-fluoro-7-(isoindol-5-yl)-8-methoxyisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210

7
[ 201940-08-1 ]
5-(9-cyclopropyl-8-methoxy-3,4-dioxo-2,3,4,9-tetrahydro-isothiazolo[5,4-b]quinolin-7-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210

8
[ 201940-08-1 ]
[ 846566-17-4 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210

9
[ 201940-08-1 ]
5-(9-cyclopropyl-6-fluoro-8-methoxy-3,4-dioxo-2,3,4,9-tetrahydro-isothiazolo[5,4-b]quinolin-7-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210

10
[ 6941-75-9 ]
[ 201940-08-1 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 199 - 210
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4909 - 4912
[3]Journal of Organic Chemistry,2012,vol. 77,p. 11296 - 11301
[4]Patent: WO2014/89324,2014,A1
[5]Patent: WO2015/54317,2015,A1
[6]Patent: CN104016979,2017,B
[7]Patent: US2017/275301,2017,A1
[8]Patent: EP3257857,2017,A1
[9]Journal of Medicinal Chemistry,2019,vol. 62,p. 7431 - 7444
[10]Patent: CN110294744,2019,A
[11]Patent: US2019/375744,2019,A1

11
[ 201940-08-1 ]
[ 292638-85-8 ]
5-(2-methoxycarbonyl-vinyl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With triethylamine; tris-(o-tolyl)phosphine;palladium diacetate; In N,N-dimethyl-formamide; at 130℃; for 15h;	To a 10OmL 3-neck round bottom flask are added 5-bromo-l,3-dihydro-isoindole-2- carboxylic acid tert-butyl ester (13.42 mmol; 1.0 equiv), Pd(OAc)2 (0.34 mmol; 0.025 equiv), and P(o-tol)3 (0.67 mmol; 0.05 equiv) and the flask is evacuated and purged with N2 three times. DMF (34 mL), methyl acrylate (14.76 mmol; 1.1 equiv), and Et3N (67.1 mmol; 5.0 equiv) are added and the reaction mixture is heated to 130 C for 15 h. The reaction is cooled to room temperature, diluted with Et2O (200 mL), and the organic layer is washed with 10% citric acid, saturated sodium hydrogen carbonate, and brine. The combined organic extracts are dried (MgSO4), filtered, and concentrated to afford the crude product, which is then purified by silica gel chromatography to yield 5-(2-methoxycarbonyl-vinyl)-l,3- dihydro-isoindole-2-carboxylic acid tert-butyl ester as a yellow solid (1.7 g; 42% yield). 1H NMR (400 MHz, CD3OD): delta 7.68 (d, J= 16 Hz, 1 H), 7.53 (m, 2 H), 7.32 (t, J= 8.0 Hz, 1 H), 6.52 (d, J= 16 Hz, 1 H), 4.64 (d, J= 8 Hz, 4 H), 3.78 (s, 3 H), 1.52 (s, 9 H). MS m/z 305.0 (M+l)+

Reference： [1]Patent: WO2008/76954,2008,A2 .Location in patent: Page/Page column 54

12
[ 109-01-3 ]
[ 201940-08-1 ]
[ 913000-37-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃;Inert atmosphere;	Synthesis of AM374-A. To a degassed mixture of tert-butyl 5-bromoisoindoline-2- carboxylate (1 g, 3.35 mmol), 1-methylpiperazine (403 mg, 4.03 mmol), Xanthphos (97 mg, 0.17 mmol) and NaOBut (482 mg, 5.03 mmol) in toluene (10 mL) was added Pd2(dba)3 (153 mg, 0.17 mmol) under N2 and the mixture was stirred at 100C overnight. The reaction mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (50 mL) and washed with brine (30 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (MeOH:CHCl3=99:1~95:5) to give AM374-A (800 mg, 75%) as a white solid
55%	With tris-(dibenzylideneacetone)dipalladium(0); johnphos; sodium t-butanolate; In toluene; at 80℃; for 4h;Inert atmosphere;	Tris(dibenzylideneacetone)dipalladium(0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added into a solution of <strong>[201940-08-1]5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester</strong> (2.97 g, 10 mmol) in toluene (15 mL). The reaction mixture was purged with argon for 5 minutes and then N-methylpiperazine (1.33 mL, 12 mmol) was added and the mixture and stirred at 80 C. for 4 hours. After the completion of the reaction (monitored by TLC) the solvent was removed under vacuum, water (3 mL) was added, and the reaction mixture was extracted with dichloromethane (3*30 mL). The combined organic extracts were dried over Na2SO4. The solvents were removed under vacuum and the residue was purified on silica gel (Biotage; eluting solvents 5% MeOH in dichloromethane) to afford tert-butyl 5-(4-methylpiperazin-1-yl)isoindoline-2-carboxylate as brown solid (1.75 g, 55% yield); 1H NMR (400 MHz, MeOH-d4) delta ppm 7.16-7.12 (m, 1H), 6.92-6.88 (m, 2H), 4.59-4.53 (m, 4H), 3.19-3.17 (m, 4H), 2.63-2.60 (m, 4H), 2.34 (s, 3H), 1.51 (9H, s).
46%	With johnphos; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 2h;	5-Bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 8O0C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1 H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.

46%	With johnphos; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 2h;	5-Bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 8O0C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.
46%	With johnphos; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 2h;	5-Bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 800C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H1 s). MS: [M+H]+ 318.
46%	With johnphos; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 2h;	5-Bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 ml.) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 8O0C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H1 m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.
46%	With johnphos; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 2h;	5-Bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 80 C. for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45 g, 46%). 1H NMR (MeOH-d4) 7.15 (1H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.

Reference： [1]Journal of Medicinal Chemistry,2020,vol. 63,p. 2139 - 2180
[2]Patent: WO2017/7756,2017,A1 .Location in patent: Paragraph 636
[3]Patent: US2019/152917,2019,A1 .Location in patent: Paragraph 0312
[4]Patent: WO2008/44029,2008,A1 .Location in patent: Page/Page column 254
[5]Patent: WO2008/44041,2008,A1 .Location in patent: Page/Page column 275-276
[6]Patent: WO2008/44045,2008,A1 .Location in patent: Page/Page column 328-329
[7]Patent: WO2008/44054,2008,A2 .Location in patent: Page/Page column 171-172
[8]Patent: US2010/152184,2010,A1 .Location in patent: Page/Page column 111
[9]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6960 - 6965

13
[ 201940-08-1 ]
[ 1445-73-4 ]
[ 913000-19-8 ]

Yield	Reaction Conditions	Operation in experiment
		0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5- bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -78C under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -78C for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia / DCM gave 111 mg of 5-(4-hydroxy-1-methyl- piperidin-4-yl)-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a colourless oil.
		0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5- bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -780C under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -780C for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia / DCM gave 111 mg of 5-(4-hydroxy-1-methyl- piperidin-4-yl)-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyi ester as a colourless oil.
		0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5- bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -78C under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -78C for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia / DCM gave 111 mg of 5-(4-hydroxy-1-methyl- piperidin-4-yl)-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a colourless oil.

		0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5- bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -78C under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -780C for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia / DCM gave 111 mg of 5-(4-hydroxy-1-methyl- piperidin-4-yl)-1 ,3-dihydro-isoindole-2-carboxyiic acid tert-butyl ester as a colourless oil.
		0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of <strong>[201940-08-1]5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester</strong> (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -78 C. under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -78 C. for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia/DCM gave 111 mg of 5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a colourless oil.

Reference： [1]Patent: WO2008/44029,2008,A1 .Location in patent: Page/Page column 235
[2]Patent: WO2008/44041,2008,A1 .Location in patent: Page/Page column 257
[3]Patent: WO2008/44045,2008,A1 .Location in patent: Page/Page column 310
[4]Patent: WO2008/44054,2008,A2 .Location in patent: Page/Page column 154
[5]Patent: US2010/152184,2010,A1 .Location in patent: Page/Page column 98
[6]Journal of Medicinal Chemistry,2010,vol. 53,p. 5956 - 5969

14
[ 201940-08-1 ]
[ 201230-82-2 ]
[ 368441-44-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With palladium diacetate; 1,3-bis-(diphenylphosphino)propane; triethylamine; In methanol; dimethyl sulfoxide; at 80℃; for 16h;	A mixture of <strong>[201940-08-1]5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester</strong> (200 mg, 0.67 mmol), Pd (OAc) 2 (30 mg, 0.2 equiv), DPPP (55 mg, 0.2 equiv), TEA (0.93 mL, 10 equiv) and MeOH : DMSO (1: 1,4 mL) was stirred for 16 h under CO (balloon) at 80 C. LC-MS and TLC (20% EtOAc-Hexane) showed completion of the reaction. The Reaction mixture was concentrated to remove MeOH and diluted with EtOAc (10 mL), and washed with water (2 x 25 mL). The organic layer was dried (Na2S04), concentrated and purified by silica gel column chromatography (eluent = 20% EtOAc-Hexane), giving pure 1, 3-dihydro-isoindole-2,5- dicarboxylic acid 2-tert-butyl ester 5-methyl ester (150 mg, 81 %). MS (APCI+) : m/z 178.1 (MH+-Boc).

Reference： [1]Patent: WO2005/37214,2005,A2 .Location in patent: Page/Page column 202

15
[ 201940-08-1 ]
[ 194366-72-8 ]
[ 1056156-64-9 ]

Yield	Reaction Conditions	Operation in experiment
	tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 50℃; for 36h;	To solution of the aryl bromide (0.200 g, 0.67 mmol) and Pd (PPh3) 4 (39 mg, 0.33 mmol) dissolved in THF under N2 was cannulated the crude vinyl zinc species from step A. The reaction was heated at 50C for 36 hours, and the then filtered through a plug of A1203 with aid of EtOAc and concentrated to give an oil which was used without further purification

Reference： [1]Patent: WO2005/37214,2005,A2 .Location in patent: Page/Page column 218

16
[ 201940-08-1 ]
[ 76-05-1 ]
[ 1059173-67-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4159 - 4162

17
[ 24424-99-5 ]
5-Bromo-isoindoline HCl salt [ No CAS ]
[ 201940-08-1 ]

Yield	Reaction Conditions	Operation in experiment
2.31 g (99%)	In pyridine; dichloromethane;	Stage 2a: N-Boc-5-Bromo-isoindoline 5-Bromo-isoindoline HCl salt (3.85 g, 16.4 mmol) was partitioned between tert-butylmethylether (100 mL) and 0.5 M aqueous sodium hydroxide (50 mL). The aqueous layer was extracted further with tert-butylmethylether (2*50 mL). The organic phases were combined, dried over anhydrous potassium carbonate, filtered, and the solvent removed under vacuum to give 1.55 g of a beige solid. The solid (1.55 g, 7.83 mmol, 1 eq) was dissolved in pyridine (2.7 mL). Di-tertbutyldicarbonate (1.78 g, 8.15 mmol, 1.05 eq.), previously dissolved in dichloromethane (6 mL) was added dropwise over 5 minutes. Stirring was continued for 15 hours at ambient temperature and the reaction mixture was concentrated to dryness. The residue was portioned between tert-butylmethylether (25 mL) and 5% aqueous citric acid solution (20 mL). The aqueous phase was discarded and the organic phase dried over sodium sulfate, filtered and the solvent removed under vacuum to give 2.31 g (99%) of a yellow oil which solidified on standing. 1H NMR (250 MHz, CHLOROFORM-d) delta ppm 7.33-7.48 (m, 2H) 7.04-7.21 (m, 1H) 4.53-4.73 (m, 4H) 1.52 (s, 9H)

Reference： [1]Patent: US2010/119479,2010,A1

18
[ 123-75-1 ]
[ 201940-08-1 ]
[ 905273-52-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6960 - 6965

19
[ 110-91-8 ]
[ 201940-08-1 ]
[ 1051394-58-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6960 - 6965

20
[ 201940-08-1 ]
4-dihydropyranyltributylstannane [ No CAS ]
[ 905274-49-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6960 - 6965

21
[ 201940-08-1 ]
[ 253801-14-8 ]

Reference： [1]Patent: WO2017/7756,2017,A1
[2]Patent: US2017/275301,2017,A1

22
[ 201940-08-1 ]
[ 149353-71-9 ]