Potassium Phosphate, Tribasic → 8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4'-(pyrrolidin-1-ylcarbonyl)biphenyl-4-yl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1423993

반응식

HRID 1423993 반응식
[Si:1]([O:8][CH2:9][C:10]1([CH3:30])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26](Cl)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N:31]1([C:36]([C:38]2[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=2)=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:1]([O:8][CH2:9][C:10]1([CH3:30])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26]([C:41]5[CH:40]=[CH:39][C:38]([C:36]([N:31]6[CH2:32][CH2:33][CH2:34][CH2:35]6)=[O:37])=[CH:43][CH:42]=5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2773571(4-(Pyrrolidine-1-carbonyl)phenyl)boronic acidHCID 867128348-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-[1-(4-chlorophenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

생성물 1

HCID 867128508-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4'-(pyrrolidin-1-ylcarbonyl)biphenyl-4-yl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine수율 91.2%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A solution of the compound (324 mg, 0.7 mmol) obtained in Example 1-2), 4-(pyrrolidin-1-ylcarbonyl)phenylboronic acid (32 mg, 0.77 mmol), tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.04 mmol), tricyclohexylphosphine (23 mg, 0.08 mmol), and tripotassium phosphate (260 mg, 1.19 mmol) in dioxane (2 mL) and water (1 mL) was stirred at 140° C. for 2 h under microwave irradiation. The reaction mixture was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 20:80, gradient) to obtain the title compound (385 mg, 91%) as a yellow oily substance.

후처리

  1. customThe reaction mixture was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 20:80, gradient)

출처 및 근거

ORD 기록
ord-2f3f59d0b5124a548094d3a4fa68e96a
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927536B2

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