Diisopropylethylamine → tert-butyl ((2S,3S)-3-((R)-hex-5-en-2-yloxy)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxopentan-2-yl)carbamate

HRID 523181Notes

Reaction equation

HRID 523181 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:21]([O:24][C@@H:25]([CH2:27][CH2:28][CH:29]=[CH2:30])[CH3:26])[CH2:22][CH3:23])[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].FC(F)(F)C(O)=O.[NH2:38][C@:39]1([C:44]([NH:46][S:47]([C:50]2([CH3:53])[CH2:52][CH2:51]2)(=[O:49])=[O:48])=[O:45])[CH2:41][C@H:40]1[CH:42]=[CH2:43].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>[CH3:26][C@@H:25]([O:24][C@@H:21]([CH2:22][CH3:23])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18](=[O:19])[NH:38][C@:39]1([C:44](=[O:45])[NH:46][S:47]([C:50]2([CH3:53])[CH2:52][CH2:51]2)(=[O:49])=[O:48])[CH2:41][C@H:40]1[CH:42]=[CH2:43])=[O:11])[CH2:27][CH2:28][CH:29]=[CH2:30]

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 90118022(2S,4R)-1-((2S,3S)-2-((tert-butoxycarbonyl)amino)-3-((R)-hex-5-en-2-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 118425558tert-butyl ((2S,3S)-3-((R)-hex-5-en-2-yloxy)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxopentan-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-((R)-hex-5-en-2-yloxy)pentanoyl)-4-hydroxypyrrolidine-2-carboxylic acid (all material from step 3, 489 mg, 1.14 mmol), (1R,2S)-1-amino-N-((1-methylcyclopropyl)sulfonyl)-2-vinylcyclopropanecarboxamide-trifluoroacetic acid salt (450 mg, 1.26 mmol), HATU (456 mg, 1.20 mmol) and DCM (10 mL). To the stirred solution was added N,N-diisopropylethylamine (0.80 mL, 4.56 mmol). The mixture was stirred for 16 h and then was transferred to a separatory funnel. The mixture was thrice washed with aq. 1N HCl; then brine. The solution was dried over MgSO4; filtered; then concentrated in vacuo to afford tert-butyl ((2S,3S)-3-((R)-hex-5-en-2-yloxy)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxopentan-2-yl)carbamate as a light-orange solid foam (569 mg).

Workup

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

Sources & evidence

ORD record
ord-bd799d67cd194a508787d62d3b871c68
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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