Diisopropylethylamine → tert-butyl (2S,3R)-1-((2S,4R)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidin-1-yl)-3-ethyl-5-methyl-1-oxonon-8-en-2-ylcarbamate

HRID 523193Notes

Reaction equation

HRID 523193 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:21]([CH2:29][CH3:30])[CH2:22][CH:23]([CH3:28])[CH2:24][CH2:25][CH:26]=[CH2:27])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18](O)=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].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.[NH2:64][C@:65]1([C:70]([NH:72][S:73]([CH:76]2[CH2:78][CH2:77]2)(=[O:75])=[O:74])=[O:71])[CH2:67][C@H:66]1[CH:68]=[CH2:69]>ClCCl>[CH:76]1([S:73]([NH:72][C:70]([C@@:65]2([NH:64][C:18]([C@@H:13]3[CH2:14][C@@H:15]([OH:17])[CH2:16][N:12]3[C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[C@H:21]([CH2:29][CH3:30])[CH2:22][CH:23]([CH3:28])[CH2:24][CH2:25][CH:26]=[CH2:27])=[O:19])[CH2:67][C@H:66]2[CH:68]=[CH2:69])=[O:71])(=[O:75])=[O:74])[CH2:78][CH2:77]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 23595125(1R,2S)-1-Amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamideHCID 86683262(2S,4R)-1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid

Product 1

HCID 86717706tert-butyl (2S,3R)-1-((2S,4R)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidin-1-yl)-3-ethyl-5-methyl-1-oxonon-8-en-2-ylcarbamateYield 87.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2S,4R)-1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid (1.3 g, 3.05 mmole) in dichloromethane (50 mL) was added HATU (1.15 g, 3.05 mmole) followed by DIPEA (1.6 mL, 9.13 mmole) at room temperature. The reaction mass was stirred at the same temperature for 10 min. (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide (1.22 g, 3.05 mmole) was added to the reaction mass and the mixture was stirred at room temperature for 1 h. The reaction mass was diluted with dichloromethane and washed with water. The organic layer was dried over anhydrous Na2SO4; filtered; then concentrated under reduced pressure to get the crude compound. The crude compound was purified by silica gel chromatography (6% methanol in chloroform) to get 1.7 g (87%) of tert-butyl (2S,3R)-1-((2S,4R)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidin-1-yl)-3-ethyl-5-methyl-1-oxonon-8-en-2-ylcarbamate as a white solid. MS: MS m/z 639.55 (M++1).

Workup

  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. concentrationthen concentrated under reduced pressure
  6. customto get the crude compound
  7. customThe crude compound was purified by silica gel chromatography (6% methanol in chloroform)

Sources & evidence

ORD record
ord-bb69aedcb4d34065bf40db3d491af1ab
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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