Diisopropylethylamine → tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate

HRID 523186Notes

Reaction equation

HRID 523186 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:21]([O:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH2:29])[CH2:22][CH3:23])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([OH:20])=O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[NH2:37][C@:38]1([C:43]([NH:45][S:46]([C:49]2([CH3:52])[CH2:51][CH2:50]2)(=[O:48])=[O:47])=[O:44])[CH2:40][C@H:39]1[CH:41]=[CH2:42].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[OH:17][C@H:15]1[CH2:16][N:12]([C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[C@@H:21]([O:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH2:29])[CH2:22][CH3:23])[C@H:13]([C:18](=[O:20])[NH:37][C@:38]2([C:43](=[O:44])[NH:45][S:46]([C:49]3([CH3:52])[CH2:51][CH2:50]3)(=[O:48])=[O:47])[CH2:40][C@H:39]2[CH:41]=[CH2:42])[CH2:14]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 90118137(2S,4R)-1-((2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoyl)-4-hydroxypyrrolidine-2-carboxylic acid2×HCID 118415166(1R,2S)-1-amino-N-((1-methylcyclopropyl)sulfonyl)-2-vinylcyclopropanecarboxamide trifluoroacetic acid salt

Product 1

HCID 118425561tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round-bottom flask equipped with a stir bar was added (2S,4R)-1-((2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoyl)-4-hydroxypyrrolidine-2-carboxylic acid (½ of material from step 3, 600 mg, 1.45 mmol), (1R,2S)-1-amino-N-((1-methylcyclopropyl)sulfonyl)-2-vinylcyclopropanecarboxamide-trifluoroacetic acid salt (571 mg, 1.59 mmol), HATU (578 mg, 1.52 mmol) and CH2Cl2 (10 mL). To the mixture was added N,N-diisopropylethylamine (1.01 mL, 5.79 mmol). The mixture was stirred at room temperature for 16 h. The mixture was transferred to a separatory funnel and was thrice washed with aq. HCl (1M); then brine. The organic solution was dried over MgSO4; filtered; then concentrated in vacuo. The resulting residue was subjected to silica gel chromatography (hexanes:acetone, 94:6 to 60:40) to afford tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate as a colorless solid foam (480 mg, 52%). MS: MS m/z 641.5 (M++1).

Workup

  1. customTo a round-bottom flask equipped with a stir bar
  2. customThe mixture was transferred to a separatory funnel
  3. washwashed with aq. HCl (1M)
  4. dry with materialThe organic solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-58a8b399c3fb424189cf64ed9332d809
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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