Diisopropylethylamine → 4-((R)-4-((R)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1476319노트

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HRID 1476319 반응식
[C:1]1([S:7][CH2:8][C@H:9]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21](=[O:24])(=[O:23])[NH2:22])=[CH:17][C:16]=2[S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[CH2:10][C:11](O)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:32]([N:34]([CH2:37][C@@H:38]1[CH2:43][O:42][CH2:41][CH2:40][N:39]1C(OC(C)(C)C)=O)[CH2:35][CH3:36])[CH3:33].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.C(OCC)(=O)C>[CH2:32]([N:34]([CH2:37][C@H:38]1[N:39]([C:11](=[O:12])[CH2:10][C@@H:9]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([NH2:22])(=[O:23])=[O:24])=[CH:17][C:16]=2[S:25]([C:28]([F:29])([F:31])[F:30])(=[O:27])=[O:26])[CH2:8][S:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:40][CH2:41][O:42][CH2:43]1)[CH2:35][CH3:36])[CH3:33]

참가 물질

7

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 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2회HCID 66723762(R)-tert-butyl 3-((diethylamino)methyl)morpholine-4-carboxylate2회

생성물 1

HCID 667235784-((R)-4-((R)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide수율 30.6%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

실험 절차

To a solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid (INTERMEDIATE 8, 500 mg, 1.00 mmol), (R)—N-ethyl-N-(morpholin-3-ylmethyl)ethanamine hydrochloride salt (INTERMEDIATE 90, 209 mg, 1.00 mmol), DIPEA (0.701 ml, 4.01 mmol) in DMA (5 ml) was added HATU (458 mg, 1.20 mmol). The mixture was stirred for 1 h at room temperature and diluted with ethyl acetate (200 ml). The mixture was washed successively with 1M aq. sodium bisulfate, saturated sodium bicarbonate, and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified column chromatography (ISCO, eluting with 0→100% DCM/10% 2 M ammonia in MeOH in DCM over 24 minutes) to give the title product (200 mg, yield: 30.5%).

후처리

  1. washThe mixture was washed successively with 1M aq. sodium bisulfate, saturated sodium bicarbonate, and brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe concentrate was purified
  6. washcolumn chromatography (ISCO, eluting with 0→100% DCM/10% 2 M ammonia in MeOH in DCM over 24 minutes)

출처 및 근거

ORD 기록
ord-5022472939b94f78a6eec096e224d5dc
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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