4-Methylmorpholine → N2-[(benzyloxy)carbonyl]-N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]alaninamide

HRID 14059

反応式

HRID 14059 の反応式
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:24]([OH:26])=O)[CH2:13][S:14]([CH:17]([CH2:21][CH2:22][CH3:23])[CH2:18][CH2:19][CH3:20])(=[O:16])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[NH2:29][C@@H:30]([CH2:44][C:45]1[CH:50]=[C:49]([F:51])[CH:48]=[C:47]([F:52])[CH:46]=1)[C@H:31]([OH:43])[CH2:32][NH:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][CH3:42])[CH:36]=1.CN1CCOCC1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:24]([NH:29][C@@H:30]([CH2:44][C:45]1[CH:46]=[C:47]([F:52])[CH:48]=[C:49]([F:51])[CH:50]=1)[C@H:31]([OH:43])[CH2:32][NH:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][CH3:42])[CH:36]=1)=[O:26])[CH2:13][S:14]([CH:17]([CH2:18][CH2:19][CH3:20])[CH2:21][CH2:22][CH3:23])(=[O:15])=[O:16])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochlorideHCID 57508140N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl)alanineHCID 178418300HCID 178418300、化合物

生成物 1

HCID 58759847N2-[(benzyloxy)carbonyl]-N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-3-[(1-propylbutyl)sulfonyl]alaninamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A 250 ml round bottom flask equipped with magnetic stir bar and N2 inlet was charged with 4.0 g (10 mmole) N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alanine and 1.2 g (12 mmole) (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride in 50 ml anhydrous methylene chloride. To the reaction mixture was added 5.6 ml (51 mmole) NMM, 1.7 g (13 mmole) hydroxybenzotriazole, and lastly 3.1 g (16 mmole) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. After stirring at room temperature for 3 hours, HPLC analysis indicated complete reaction. The reaction was diluted with methylene chloride and washed with saturated sodium bicarbonate solution, 0.5 M citric acid, and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give the N2-[(benzyloxy)carbonyl]-N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]alaninamide. A 50 ml round bottom flask equipped with magnetic stir bar and N2 inlet was charged with the crude residue in anhydrous methylene chloride. The reaction was cooled to 0° C. and added 2.5 g (12 mmole) di-tert-butyl dicarbonate and 1.2 ml (11 mmole) N-methyl morpholine. The reaction was allowed to warm to room temperature and stirred for 18 hours at which point HPLC analysis indicated complete reaction. The reaction was diluted with methylene chloride and washed with saturated sodium bicarbonate solution, and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified on silica gel by flash chromatography using a gradient solvent of 5-40% ethyl acetate in hexane to give 3.4 g of N2-[(benzyloxy-)carbonyl]-N1-{(1S,2R)-N-[(t-butyloxy)carbonyl]-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1-propylbutyl)sulfonyl]-D,L-alaninamide. M+Na=824.

後処理

  1. customA 250 ml round bottom flask equipped with magnetic stir bar and N2 inlet
  2. customreaction
  3. washwashed with saturated sodium bicarbonate solution, 0.5 M citric acid, and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-91f4776e98b348aeba464b8d72a437ce
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

関連ノート

読み込み中…