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

HRID 1476315ノート

反応式

HRID 1476315 の反応式
[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]

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 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2 回HCID 66723823(S)-tert-butyl 3-((diethylamino)methyl)morpholine-4-carboxylate2 回

生成物 1

HCID 667236584-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide収率 58.2%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino) butanoic acid (INTERMEDIATE 8, 500 mg, 1.00 mmol), (S)—N-ethyl-N-(morpholin-3-ylmethyl)ethanamine hydrochloride salt (INTERMEDIATE 86, 50 mg, 1.2 mmol), DIPEA (0.526 ml, 3.01 mmol), in DMA (5 ml) was added HATU (458 mg, 1.20 mmol). The mixture was stirred for 1 hour at room temperature and diluted with ethyl acetate (200 ml). The mixture was washed successively with 1 M 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 (380 mg, yield: 58%).

後処理

  1. washThe mixture was washed successively with 1 M 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)

出典と根拠

ORDレコード
ord-a64954df703c4a36948fc378555e4815
出典データセット
uspto-grants-2015_04
特許番号
US09018381B2

反応ノート

読み込み中…