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 1852186Notes

Reaction equation

HRID 1852186 reaction equation
[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

Participants

6

Reactant 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

Product 1

HCID 89182300tert-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)carbamateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-d12741a112654c41b592e01a90d26a2f
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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