Diisopropylethylamine → 4-[1-benzenesulfonyl-5-(3-benzyloxycarbonylamino-2,2-difluoro-propionylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1257637ノート

反応式

HRID 1257637 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:20]([NH2:21])=[CH:19][N:18]=[C:17]3[N:22]([S:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH:23]=[CH:24][C:16]=23)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:34]([O:41][C:42]([NH:44][CH2:45][C:46]([F:51])([F:50])[C:47](O)=[O:48])=[O:43])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH3:8].[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:15]2[C:20]([NH:21][C:47](=[O:48])[C:46]([F:51])([F:50])[CH2:45][NH:44][C:42]([O:41][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:43])=[CH:19][N:18]=[C:17]3[N:22]([S:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)(=[O:26])=[O:27])[CH:23]=[CH:24][C:16]=23)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 226353073-Benzyloxycarbonylamino-2,2-difluoropropionic acidHCID 673232814-(5-Amino-1-benzenesulfonyl 1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

生成物 2

HCID 222Ammonia収率 0%HCID 673530054-[1-benzenesulfonyl-5-(3-benzyloxycarbonylamino-2,2-difluoro-propionylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester収率 317.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.06 mmol), 3-benzyloxycarbonylamino-2,2-difluoro-propionic acid (300 mg, 1.15 mmol), diisopropylethylamine (363 μL, 2.12 mmol) and HATU (440 mg, 1.15 mmol) in DCM (10 mL) was stirred at ambient temperature for 3.5 hours. The reaction mixture was concentrated under vacuum and the residue purified by column chromatography on silica gel (gradient: 0 to 5% methanol in DCM then 0 to 10% 2M NH3 in methanol solution in DCM) to afford 1.20 g of 4-[1-benzenesulfonyl-5-(3-benzyloxycarbonylamino-2,2-difluoro-propionylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester. LCMS (Method B, ESI): RT=3.91 min, m+H=713.

後処理

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue purified by column chromatography on silica gel (gradient

出典と根拠

ORDレコード
ord-51809884b7f44ca5aef39fd81485828c
出典データセット
uspto-grants-2013_06
特許番号
US08461328B2

反応ノート

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