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Diisopropylethylamine → tert-butyl ((3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-((4-ethoxyisoquinolin-1-yl)oxy)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate

HRID 1852186
ノート
印刷プレビュー

反応式

HRID 1852186 の反応式
[C:1]([O:5][C:6]([NH:8][CH:9]([C@H:34]([CH3:42])[CH2:35][CH:36]([CH3:41])[CH2:37][CH2:38][CH:39]=[CH2:40])[C:10]([N:12]1[CH2:16][C@H:15]([O:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]([O:28][CH2:29][CH3:30])=[CH:20][N:19]=2)[CH2:14][C@H:13]1[C:31](O)=[O:32])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].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.Cl.[NH2:77][C@:78]1([C:83]([NH:85][S:86]([CH:89]2[CH2:91][CH2:90]2)(=[O:88])=[O:87])=[O:84])[CH2:80][C@H:79]1[CH:81]=[CH2:82]>ClCCl>[CH:89]1([S:86]([NH:85][C:83]([C@@:78]2([NH:77][C:31]([C@@H:13]3[CH2:14][C@@H:15]([O:17][C:18]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[C:21]([O:28][CH2:29][CH3:30])=[CH:20][N:19]=4)[CH2:16][N:12]3[C:10](=[O:11])[CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[C@H:34]([CH3:42])[CH2:35][CH:36]([CH3:41])[CH2:37][CH2:38][CH:39]=[CH2:40])=[O:32])[CH2:80][C@H:79]2[CH:81]=[CH2:82])=[O:84])(=[O:88])=[O:87])[CH2:91][CH2:90]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

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 23595124(1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochlorideHCID 86683246(2S,4R)-1-((3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-((4-ethoxyisoquinolin-1-yl)oxy)pyrrolidine-2-carboxylic acid

生成物 1

HCID 89182300
tert-butyl ((3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-((4-ethoxyisoquinolin-1-yl)oxy)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate
収率 61%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (2S,4R)-1-((3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-((4-ethoxyisoquinolin-1-yl)oxy)pyrrolidine-2-carboxylic acid (600 mg, 1.0 mmole) in dichloromethane (10 mL) was added DIPEA (0.87 mL, 5 mmole), HATU (380 mg, 1.0 mmole) followed by (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochloride (prepared according to the procedure described in WO 03/099274) (457 mg, 1.1 mmole) at room temperature. The reaction mixture was stirred at room temperature for 2 h. The reaction mass was diluted with DCM and washed with water. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography to get desired product tert-butyl ((3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-((4-ethoxyisoquinolin-1-yl)oxy)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (500 mg, 61%) as off-white solid. MS: MS m/z 797.2 (M++1).

後処理

  1. customprepared
  2. customat room temperature
  3. washwashed with water
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto get crude compound
  7. customThe crude compound was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-d12741a112654c41b592e01a90d26a2f
出典データセット
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08957203B2

反応ノート

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