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Diisopropylethylamine → benzyl (S)-1-((S)-1-((S)-2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(2-(methylsulfonyl)ethyl)carbamate

HRID 627048
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HRID 627048 반응식
[NH2:1][C@@H:2]([CH:25]([CH3:27])[CH3:26])[C:3]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH2:7][C@H:6]1[C:14]([NH:16][C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1[F:24])=[O:15])=[O:4].[CH2:28]([O:35][C:36]([N:38]([CH2:44][CH2:45][S:46]([CH3:49])(=[O:48])=[O:47])[C@@H:39]([CH3:43])[C:40](O)=[O:41])=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[NH:16][C:14]([C@H:6]1[N:5]([C:3](=[O:4])[C@@H:2]([NH:1][C:40](=[O:41])[C@@H:39]([N:38]([CH2:44][CH2:45][S:46]([CH3:49])(=[O:48])=[O:47])[C:36](=[O:37])[O:35][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH3:43])[CH:25]([CH3:27])[CH3:26])[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH2:7]1)=[O:15]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 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 117871199HCID 117871199, 화합물2회HCID 117871606(S)-1-((S)-2-amino-3-methylbutanoyl)-N-(2,6-difluorophenyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carb ox amide2회

생성물 1

HCID 131735267
benzyl (S)-1-((S)-1-((S)-2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(2-(methylsulfonyl)ethyl)carbamate
수율 62.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

In a 50 mL round-bottomed flask, (S)-1-((S)-2-amino-3-methylbutanoyl)-N-(2,6-difluorophenyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carb ox amide (Intermediate 6) (29 mg, 77.5 μmol, Eq: 1.00), (S)-2-((benzyloxycarbonyl)(2-(methylsulfonyl)ethyl)amino)propanoic acid (Intermediate 9) (30.6 mg, 93.0 μmol, Eq: 1.2), HATU (35.3 mg, 93.0 μmol, Eq: 1.2) and diisopropylethylamine (16 μL, 93.0 μmol, Eq: 1.2) were combined with DMF (2 mL) to give a colorless solution. The reaction mixture was stirred at rt overnight and then partitioned between EtOAc and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 4 g, 0% to 50% EtOAc in hexanes) to give benzyl (S)-1-((S)-1-((S)-2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(2-(methylsulfonyl)ethyl)carbamate (33 mg).

후처리

  1. customto give a colorless solution
  2. custompartitioned between EtOAc and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 4 g, 0% to 50% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-7508fabf53914b619097259fed325289
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09309248B2

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