Triethylamine → (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-2-(4-hydroxy-2-methylbutan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide

HRID 468525노트

반응식

HRID 468525 반응식
[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([OH:16])=O)[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[NH2:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][C:27]=1[F:28])[N:24]([CH2:29][C@@H:30]1[CH2:34][O:33][C:32]([CH3:36])([CH3:35])[O:31]1)[C:23]([C:37]([CH3:42])([CH3:41])[CH2:38][CH2:39][OH:40])=[CH:22]2.NC1C=C2C(=CC=1F)NC(C(C)(C)CCO)=C2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[F:17][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:18][C:19]4[CH:20]=[C:21]5[C:25](=[CH:26][C:27]=4[F:28])[N:24]([CH2:29][C@@H:30]4[CH2:34][O:33][C:32]([CH3:35])([CH3:36])[O:31]4)[C:23]([C:37]([CH3:42])([CH2:38][CH2:39][OH:40])[CH3:41])=[CH:22]5)=[O:16])[CH2:12][CH2:13]3)=[CH:10][C:4]=2[O:3]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 442061031-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxylic acidHCID 58201776(R)-3-(5-amino-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-olHCID 670446163-(5-amino-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol

생성물 1

HCID 67044201(R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-2-(4-hydroxy-2-methylbutan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (183 mg, 0.75 mmol), (R)-3-(5-amino-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol containing some 3-(5-amino-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol (220 mg, 0.63 mmol) and HATU (287 mg, 0.75 mmol) in DMF (3.0 mL) was added triethylamine (0.21 mL, 1.5 mmol). The reaction was stirred at room temperature overnight and then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (20-40% ethyl acetate-hexanes) to afford (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-2-(4-hydroxy-2-methylbutan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (315 mg, 87%, contains some 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-fluoro-2-(4-hydroxy-2-methylbutan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide). ESI-MS m/z calc. 574.2 found 575.7 (M+1)+. Retention time 2.08 minutes.

후처리

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal of solvent
  6. customthe residue was purified by column chromatography (20-40% ethyl acetate-hexanes)

출처 및 근거

ORD 기록
ord-8c83ee263db24d33a9a9a0f5739b06b8
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623905B2

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