[ CAS No. 1035235-27-8 ] {[proInfo.proName]}

Name: 1035235-27-8|tert-Butyl 4-bromoisoindoline-2-carboxylate|95%
Brand: Ambeed
SKU: A152606
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Quality Control of [ 1035235-27-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1035235-27-8 ]

Product Details of [ 1035235-27-8 ]

CAS No. :	1035235-27-8	MDL No. :	MFCD10700130
Formula :	C₁₃H₁₆BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BFCZVUVSPUKWET-UHFFFAOYSA-N
M.W :	298.18	Pubchem ID :	49853504
Synonyms :

Calculated chemistry of [ 1035235-27-8 ]

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) :	3.25
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 :	2.98

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 :	2.31

Safety of [ 1035235-27-8 ]

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

Application In Synthesis of [ 1035235-27-8 ]

* 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 [ 1035235-27-8 ]
Downstream synthetic route of [ 1035235-27-8 ]

[ 1035235-27-8 ] Synthesis Path-Upstream 1~3

1
[ 923590-95-8 ]
[ 24424-99-5 ]
[ 1035235-27-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine In tetrahydrofuran at 10 - 20℃; for 12 h;	Step e. TEA (126 ml, 903 mmol) was added drop-wise over 5 min to a stirred suspension of 4- bromoisoindoline HQ (100 g, 430 mmol) in THF (700 ml) and the mixture was cooled to 10°C. The cooled mixture was then treated with a solution of di-tert-butyl dicarbonate (122 g, 559 mmol) in THF (300 ml) over 15 min whilst maintaining the temperature below 20°C, and the resulting mixture was stirred at rt for 12 h. The reaction was concentrated under vacuum to give an oil, which was partitioned between EtOAc (600 ml) and water (600 ml). The aqueous phase was collected and extracted with EtOAc (2 χ 500 ml), and the combined organic extracts were washed with brine, dried over Na2S04, filtered and evaporated to dryness under vacuum to give the crude product as a solid (161 g). The crude solid was slurried in hexane (150 ml), filtered and the resulting solid washed with hexane (60 ml) before being dried under vacuum at rt to give the desired product as a solid (95.7 g, 75percent). LCMS (Method R): rt 3.02 min, m/z 242 (-tBu)/198(-Boc) [M+H]+; NMR (400 MHz, DMSO-d6) δ ppm 7.51-7.46 (dd, J = 7.8, 0.6 Hz, 1H), 7.38-730 (m, 1H), 7.29-7.21 (m, 1H), 4.73- 4.63 (d, 2H), 4.56-4.47 (d, 2H), 1.50-1.42 (d, 9H).

Reference： [1] Patent: WO2017/158388, 2017, A1, . Location in patent: Page/Page column 55; 214
[2] Journal of Organic Chemistry, 2017, vol. 82, # 14, p. 7576 - 7582

2
[ 24424-99-5 ]
[ 1035235-27-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 18 h;	A solution of 4-bromoisoindoline hydrochloride (1.40 g, 5.97 mmol) in DMF (30 mL) was treated with triethylamine (2.50 mL, 17.9 mmol) and di-tert-butyl dicarbonate (2.08 mL, 8.95 mmol), and the mixture was stirred at room temperature for 18 h. Themixture was diluted with EtOAc (65 mL) and washed three times with saturated aqueousNaHCO3. The organic phase was dried and concentrated. The residue was subjected tocolumn chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 0-3 0percent), to provide tert-butyl 4-bromoisoindoline-2-carboxylate as a white solid (1.70 g,91percent yield).

Reference： [1] Patent: WO2016/65236, 2016, A1, . Location in patent: Page/Page column 118

3
[ 127168-81-4 ]
[ 24424-99-5 ]
[ 1035235-27-8 ]

Reference： [1] Patent: US2008/171754, 2008, A1, . Location in patent: Page/Page column 104

[ 1035235-27-8 ] Synthesis Path-Downstream 1~49

1
[ 127168-81-4 ]
[ 24424-99-5 ]
[ 1035235-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In tetrahydrofuran; water; at 20℃;	Step 4: tert-butyl 4-bromo-1,3-dihydro-2H-isoindole-2-carboxylate To a solution of 4-bromoisoindolin-1-one (4 mmol) in THF (8 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 (2 mL) and then 3N HCl. The reaction mixture was allowed to stir at reflux for 3 hr and then concentrated. Water was added to the residue and the pH of the solution was adjusted to >9 with 4N NaOH. The solution was extracted with diethyl ether. The organic solutions from this basic extraction were combined, dried over Na2SO4, filtered and concentrated to give 4-bromoisoindoline, which was dissolved in THF (5 mL). To this solution was added potassium carbonate (4 mmol) in water (0.5 mL), and BOC2O (2 mmol). The reaction mixture was allowed to stir at rt overnight. 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 4-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.8 mmol, 20%).

Reference： [1]Patent: US2008/171754,2008,A1 .Location in patent: Page/Page column 104

2
[ 1035235-27-8 ]
[ 73183-34-3 ]
[ 1035235-28-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 6.0h;Inert atmosphere;	Step f. Bis(pinacolato)diboron (87.5 g, 344 mmol) was added to a solution of tert-butyl 4- bromoisoindoline-2-carboxylate (85.6 g, 287 mmol) in 1,4-dioxane (850 ml), followed by potassium acetate (56.2 g, 574 mmol), and the resulting mixture was degassed with nitrogen for 15 min. Pd(dppf)Cl2 (21 g, 28.7 mmol) was added to the reaction flask and the resulting mixture was heated at 100C for 6 h. Upon completion of the reaction, as determined by LCMS, the mixture was cooled to rt and filtered through a pad of Celite, washing with EtOAc (2 chi 50 ml). The filtrate was evaporated to dryness under vacuum to give a black oily residue, which was dissolved in DCM and passed through a silica pad, eluting with DCM. The solvent was subsequently removed under vacuum to give a solid, which was triturated with hexane (200 ml) and dried under vacuum at rt to give the desired product as a white solid (88 g, 89%). LCMS (Method R): rt 3.36 min, m/z 346, 290 (-iBu), 246 (-Boc) [M+H]+; NMR (400 MHz, DMSO-d6) delta ppm 7.62-7.54 (m, 1H), 7.48-7.41 (m, 1H), 7.33-7.25 (m, 1H), 4.70-4.62 (m, 2H), 4.60-4.53 (m, 2H), 1.49-1.43 (m, 9 H), 1.33-1.27 (m, 12 H).
80%	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 85℃; for 4.0h;	Step 5: tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate A solution of <strong>[1035235-27-8]tert-butyl 4-bromo-1,3-dihydro-2H-isoindole-2-carboxylate</strong> (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 to give tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate (0.64 mmol, 80%) as a white solid. LCMS: (FA) ES+346.
76%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃;Inert atmosphere;	A mixture of <strong>[1035235-27-8]tert-butyl 4-bromoisoindoline-2-carboxylate</strong> (1.70 g, 5.70 mmol),4,4,4?,4?,5 ,5 ,5 ?,S ?-octamethyl-2,2?-bi(1 ,3 ,2-dioxaborolane) (1.74 g, 6.84 mmol), potassiumacetate (1.68 g, 17.1 mmol), and PdC12(dppf) DCM adduct (0.466 g, 0.570 mmol) in 1,4-dioxane (25 mL) was bubbled with nitrogen and stirred at 80 C overnight. The mixture was cooled to room temperature, diluted with EtOAc, washed with water, dried and concentrated. The residue was subjected to colunm chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 0-30%), to provide tert-butyl 4-(4,4,5 ,5 -tetramethyl5 1 ,3,2-dioxaborolan-2-yl)isoindoline-2-carboxylate as a white solid (1.50 g, 76% yield).

1.2 g

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90℃; for 16.0h;Inert atmosphere;

A mixture of <strong>[1035235-27-8]tert-butyl 4-bromoisoindoline-2-carboxylate</strong> (1.00 g, 3.37mmol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1 ,3,2-dioxaborolane) (1.03 g, 4.04 mmol), AcOK (661 mg, 6.74 mmol) and Pd(dppf)C12 (50.0 mg) in dioxane (20 mL) was stirred at 90C lbr 16 h under the nitrogen atmosphere. After cooling down to 20C and LCMS showed the reaction was complete, the mixture was filtered and the filtrate was concentrated under reduced pressure to get the title compound (1.2 g, yield 103%) as a brown solid, which was directly to the next step without further purification ?HNMR(CDC13, 400 MHz) oe 7.69 (d, J 7.2 Hz, 1 H) 7.36-7.27 (m, 2 H) 4.87-4.63 (m, 4 H) 1.52 (s, 9 H) 1.31 (s, 12 H).

Reference： [1]Patent: WO2017/158388,2017,A1 .Location in patent: Page/Page column 55; 214
[2]Patent: US2008/171754,2008,A1 .Location in patent: Page/Page column 104
[3]Patent: WO2016/65236,2016,A1 .Location in patent: Page/Page column 118; 119
[4]Patent: WO2015/54317,2015,A1 .Location in patent: Paragraph 0288; 0289

3
[ 1035235-27-8 ]
[ 1434720-26-9 ]
[(S)-1-(2,4-difluoro-3-phenoxy-phenyl)-propyl]-(2,3-dihydro-1H-isoindol-4-yl)-amine hydrochloride [ No CAS ]

Reference： [1]Patent: WO2013/64538,2013,A1

4
[ 1035235-27-8 ]
[ 1434720-26-9 ]
[ 1434816-15-5 ]

Yield	Reaction Conditions	Operation in experiment
23 mg	With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In 1,4-dioxane; at 120℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	Example 136 r(S)-1-(2.4-Difluoro-3-phenoxy-phenyl)-propy\|1-(2,3-dihydro-1 H-isoindol-4-yl)-am hydrochlorideStep 1 A solution of Key Intermediate 1 (50 mg, 0.19 mmol), fe -butyl 4- bromoisoindoline-2-carboxylate (57 mg, 0.19 mmol) and sodium fe -butoxide (26 mg, 0.27 mmol) in dioxane (1 ml) was degassed by bubbling through nitrogen for 5 mins. Tris(dibenzylideneacetone)dipalladium (0) (5 mg) and 2,2'-bis(diphenylphosphino)-1 ,1 '- binapthyl (5 mg) were added and the reaction mixture was heated to 120 C for 20 mins under microwave irradiation. The mixture was partitioned between sat. sodium hydrogen carbonate and ethyl acetate. The organic fractions were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by preparative hplc to give 4-[(S)-1-(2,4-difluoro-3-phenoxy-phenyl)-propylamino]-1 ,3-dihydro-isoindole-2- carboxylic acid tert-butyl ester (23 mg) as a solid.

Reference： [1]Patent: WO2013/64538,2013,A1 .Location in patent: Page/Page column 158; 159

5
[ 1035235-27-8 ]
[ 871013-92-2 ]

Reference： [1]Patent: WO2015/54317,2015,A1

6
[ 1035235-27-8 ]
tert-butyl 4-methoxyisoindoline-2-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/54317,2015,A1

7
[ 1035235-27-8 ]
[ 127168-73-4 ]

Reference： [1]Patent: WO2015/54317,2015,A1

8
[ 1035235-27-8 ]
N-(2-(4-methoxyisoindolin-2-yl)pyrimidin-4-yl)-1H-indazol-5-amine [ No CAS ]

Reference： [1]Patent: WO2015/54317,2015,A1

9
[ 1035235-27-8 ]
(RS)-3-fluoro-4-(isoindolin-4-yl)-9H-carbazole-1-carboxamide trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2016/65236,2016,A1

10
[ 1035235-27-8 ]
tert-butyl 4-(1-carbamoyl-3-fluoro-9H-carbazol-4-yl)isoindoline-2-carboxylate [ No CAS ]

Reference： [1]Patent: WO2016/65236,2016,A1

11
[ 24424-99-5 ]
4-bromoisoindoline hydrochloride [ No CAS ]
[ 1035235-27-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 18.0h;	A solution of 4-bromoisoindoline hydrochloride (1.40 g, 5.97 mmol) in DMF (30 mL) was treated with triethylamine (2.50 mL, 17.9 mmol) and di-tert-butyl dicarbonate (2.08 mL, 8.95 mmol), and the mixture was stirred at room temperature for 18 h. Themixture was diluted with EtOAc (65 mL) and washed three times with saturated aqueousNaHCO3. The organic phase was dried and concentrated. The residue was subjected tocolumn chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 0-3 0%), to provide tert-butyl 4-bromoisoindoline-2-carboxylate as a white solid (1.70 g,91% yield).

Reference： [1]Patent: WO2016/65236,2016,A1 .Location in patent: Page/Page column 118

12
[ 1035235-27-8 ]
[ 19438-10-9 ]
tert-butyl 4-(3-(methoxycarbonyl)phenoxy)isoindoline-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With potassium phosphate; palladium diacetate; tert-butyl XPhos; In toluene; at 115℃; for 16.0h;Inert atmosphere;	tert-Butyl 4-bromoisoindoline-2-carboxylate (163 mg, 0.548 mmol), methyl 3-hydroxybenzoate (100 mg, 0.657 mmol), di-tert-butyl(2?,4?,6?-triisopropyl-[1,1?-biphenylj-2-yl)phosphine (23 mg, 0.055 mmol), palladium(II) acetate (12 mg, 0.055 mmol) and potassium phosphate (233 mg, 1.10 mmol) were added to a vial, which was then evacuated and back-filled with argon three times. Degassed toluene (1.8 mL) was added. The reaction mixture was stirred at 115 C for 16 h. The reaction mixture wasdiluted with DCM, filtered, and purified by flash chromatography to give 231A (55 mg,27%) as a colorless oil. MS(ESI) m/z 269.9 (M-Boc+H).

Reference： [1]Patent: WO2017/40449,2017,A1 .Location in patent: Paragraph 00541

13
[ 923590-95-8 ]
[ 24424-99-5 ]
[ 1035235-27-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine; In dichloromethane; at 0 - 20℃; for 3.0h;Inert atmosphere;	General procedure: 4-Bromoisoindoline hydrochloride (3.0 g, 13 mmol, 1 eq) was suspended in dry DCM (50 ml), and then TEA (5.4 ml, 39 mmol, 3 eq) was added. Reaction mixture was cooled to 0C in an ice-bath, and then benzyl chloroformate (2.7 ml, 19 mmol, 1 .5 eq) dissolved in 10 ml DCM was added dropwise. Reaction was carried out under inert gas (nitrogen) atmosphere while stirring at room temperature for 3h. Reaction mixture was extracted thrice with saturated NaHCC solution, then once with water and with saturated NaCl solution. Organic phase was dried over anhydrous Na2S04, and then concentrated under reduced pressure to obtain white solid which was dried under vacuum. (0165) White solid, yield: 90% (3.8 g), Ci6Hi4BrN02, MW 332.19, monoisotopic mass 331 .02, [M+H]+ 332.2, UPLC Rt = 8.12. 1H NMR (300 MHz, CDCU) d (ppm) 4.73 (dd, J= 1 1 .6, 1 .4 Hz, 2H), 4.79-4.89 (m, 2H), 5.22 (d, J = 2.2 Hz, 2H), 7.09-7.50 (m, 7H).
75%	With triethylamine; In tetrahydrofuran; at 10 - 20℃; for 12.0h;	Step e. TEA (126 ml, 903 mmol) was added drop-wise over 5 min to a stirred suspension of 4- bromoisoindoline HQ (100 g, 430 mmol) in THF (700 ml) and the mixture was cooled to 10C. The cooled mixture was then treated with a solution of di-tert-butyl dicarbonate (122 g, 559 mmol) in THF (300 ml) over 15 min whilst maintaining the temperature below 20C, and the resulting mixture was stirred at rt for 12 h. The reaction was concentrated under vacuum to give an oil, which was partitioned between EtOAc (600 ml) and water (600 ml). The aqueous phase was collected and extracted with EtOAc (2 chi 500 ml), and the combined organic extracts were washed with brine, dried over Na2S04, filtered and evaporated to dryness under vacuum to give the crude product as a solid (161 g). The crude solid was slurried in hexane (150 ml), filtered and the resulting solid washed with hexane (60 ml) before being dried under vacuum at rt to give the desired product as a solid (95.7 g, 75%). LCMS (Method R): rt 3.02 min, m/z 242 (-tBu)/198(-Boc) [M+H]+; NMR (400 MHz, DMSO-d6) delta ppm 7.51-7.46 (dd, J = 7.8, 0.6 Hz, 1H), 7.38-730 (m, 1H), 7.29-7.21 (m, 1H), 4.73- 4.63 (d, 2H), 4.56-4.47 (d, 2H), 1.50-1.42 (d, 9H).
75%	With triethylamine; In dichloromethane; at 0 - 20℃;	A solution of 4-bromoisoindoline hydrochloride (8.00 g, 34.33 mmol) in dichloromethane (20 mL) and triethylamine (14.3 mL, 103.0 mmol) was cooled to 0 C, and then di-tert-butyl dicarbonate (15.0 g, 68.73 mmol) was added. The mixture stirred overnight at room temperature and was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3x50 mL of dichloromethane, washed with 1x50 mL of brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with ethyl acetate/petroleum ether (1 :5)) to afford tert-butyl 4-bromoisoindoline-2-carboxylate (9 g, 75%) as a white solid. MS: (ESI, m/z): 242 [M-t-Bu+H]+

Reference： [1]Patent: WO2019/97282,2019,A1 .Location in patent: Page/Page column 11; 12
[2]Patent: WO2017/158388,2017,A1 .Location in patent: Page/Page column 55; 214
[3]Patent: WO2019/204550,2019,A1 .Location in patent: Paragraph 00130
[4]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

14
[ 1035235-27-8 ]
tert-butyl 4-ethynylisoindoline-2-carboxylate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

15
[ 1035235-27-8 ]
4-ethynylisoindoline hydrochloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

16
[ 1035235-27-8 ]
(3R,5S)-1-((S)-2-((((2,2-dimethylbut-3-yn-1-yl)oxy)carbonyl)-amino)-3,3-dimethylbutanoyl)-5-(methoxycarbonyl)-pyrrolidin-3-yl 4-ethynylisoindoline-2-carboxylate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

17
[ 1035235-27-8 ]
C₃₀H₃₅N₃O₇ [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

18
[ 1035235-27-8 ]
[ 923591-06-4 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

19
[ 1035235-27-8 ]
[ 1066-54-2 ]
tert-butyl 4-((trimethylsilyl)ethynyl)isoindoline-2-carboxylate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 7576 - 7582

20
[ 1035235-27-8 ]
3-amino-N-methylisoquinoline-6-carboxamide trifluoroacetate [ No CAS ]
tert-butyl 4-((6-(methylcarbamoyl)isoquinolin-3-yl)amino)isoindoline-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.135 g	With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 105℃; for 2.0h;Inert atmosphere;	Step a. A suspension of 3-amino-N-methylisoquinoline-6-carboxamide TFA salt (Intermediate 6, 0.40 g, 1.262 mmol), <strong>[1035235-27-8]tert-butyl 4-bromoisoindoline-2-carboxylate</strong> (Intermediate 1, 0.15 g, 0.505 mmol), and potassium tert-butoxide (0.28 g, 2.525 mmol) in toluene (10 ml) was degassed with nitrogen for 10 min at rt. BetaIotaNuAlphaRho (0.047 g, 0.050 mmol) and Pd2(dba)3 (0.032 g, 0.050 mmol) were added to the reaction mixture at rt. The reaction mixture was heated at 105C for 2 h. The resulting reaction mixture was cooled to rt, poured into water (20 ml) and extracted with EtOAc (2 x 40 ml). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (4% MeOH in DCM) yielding tert-butyl 4-((6-(methylcarbamoyl)isoquinolin-3-yl)amino)isoindoline-2-carboxylate (0.135 g, 0.322 mmol). LCMS: Method A, 2.278 min, MS: ES+ 419.5.

Reference： [1]Patent: WO2017/158388,2017,A1 .Location in patent: Page/Page column 80

21
[ 1035235-27-8 ]
C₂₁H₂₀FN₃O₃ [ No CAS ]