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

HRID 1852180노트

반응식

HRID 1852180 반응식
[CH:1]1([S:4]([NH:7][C:8]([C@@:10]2([NH:15][C:16]([C@@H:18]3[CH2:22][C@@H:21]([O:23][C:24]4[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[C:27]([O:34][CH3:35])=[CH:26][N:25]=4)[CH2:20][NH:19]3)=[O:17])[CH2:12][C@H:11]2[CH:13]=[CH2:14])=[O:9])(=[O:6])=[O:5])[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:69]([O:73][C:74]([NH:76][CH:77]([C@H:81]([CH3:89])[CH2:82][CH:83]([CH3:88])[CH2:84][CH2:85][CH:86]=[CH2:87])[C:78](O)=[O:79])=[O:75])([CH3:72])([CH3:71])[CH3:70]>ClCCl>[CH:1]1([S:4]([NH:7][C:8]([C@@:10]2([NH:15][C:16]([C@@H:18]3[CH2:22][C@@H:21]([O:23][C:24]4[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[C:27]([O:34][CH3:35])=[CH:26][N:25]=4)[CH2:20][N:19]3[C:78](=[O:79])[CH:77]([NH:76][C:74](=[O:75])[O:73][C:69]([CH3:72])([CH3:71])[CH3:70])[C@H:81]([CH3:89])[CH2:82][CH:83]([CH3:88])[CH2:84][CH2:85][CH:86]=[CH2:87])=[O:17])[CH2:12][C@H:11]2[CH:13]=[CH2:14])=[O:9])(=[O:6])=[O:5])[CH2:2][CH2:3]1

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 86683236(3R)-2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoic acidHCID 86683238(2S,4R)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-4-((4-methoxyisoquinolin-1-yl)oxy)pyrrolidine-2-carboxamide

생성물 1

HCID 86683239tert-butyl ((3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-((4-methoxyisoquinolin-1-yl)oxy)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (2S,4R)—N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-4-((4-methoxyisoquinolin-1-yl)oxy)pyrrolidine-2-carboxamide (595 mg, 1.9 mmol) in dichloromethane (15 mL) was added HATU (755 mg, 1.9 mmol) followed by DIPEA (1.7 mL, 9.9 mmole) at room temperature. The reaction mass was stirred at the same temperature for 10 min. (3R)-2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoic acid (1.0 g, 1.9 mmole) was added to the reaction mass and the solution was stirred at room temperature for 30 min. The reaction mass was diluted with dichloromethane and washed with water. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to get the crude compound. The crude compound was purified by silica gel chromatography (70% ethyl acetate in pet ether) to get desired product tert-butyl ((3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-((4-methoxyisoquinolin-1-yl)oxy)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate as a pale yellow solid. MS: MS m/z 782.1 (M++1).

후처리

  1. additionwas added to the reaction mass
  2. washwashed with water
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto get the crude compound
  7. customThe crude compound was purified by silica gel chromatography (70% ethyl acetate in pet ether)

출처 및 근거

ORD 기록
ord-d2b86daeaacd427d9c98692983f698a2
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957203B2

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