Water → tert-butyl (3S)-3-{[(2S)-2-(2-{[2-({[(tert-butoxy)carbonyl]amino}methyl)-1,3-thiazol-4-yl]formamido}-2-methylpropanamido)-3-methylbutanoyl]oxy}pent-4-enoate

HRID 1485847Notes

Reaction equation

HRID 1485847 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:11][CH:12]=[C:13]([C:15]([NH:17][C:18]([CH3:23])([CH3:22])[C:19]([OH:21])=O)=[O:16])[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[NH2:33][C@@H:34]([CH:49]([CH3:51])[CH3:50])[C:35]([O:37][C@H:38]([CH:47]=[CH2:48])[CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[O:36].O>CN(C)C=O.CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:11][CH:12]=[C:13]([C:15]([NH:17][C:18]([CH3:23])([CH3:22])[C:19]([NH:33][C@@H:34]([CH:49]([CH3:51])[CH3:50])[C:35]([O:37][C@H:38]([CH:47]=[CH2:48])[CH2:39][C:40]([O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:41])=[O:36])=[O:21])=[O:16])[N:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 25053306(S)-tert-butyl 3-((S)-2-amino-3-methylbutanoyloxy)pent-4-enoateHCID 679919852-(2-((Tert-butoxycarbonylamino)methyl)thiazole-4-carboxamido)-2-methylpropanoic acid

Product 1

HCID 86691464tert-butyl (3S)-3-{[(2S)-2-(2-{[2-({[(tert-butoxy)carbonyl]amino}methyl)-1,3-thiazol-4-yl]formamido}-2-methylpropanamido)-3-methylbutanoyl]oxy}pent-4-enoateYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(2-((tert-butoxycarbonylamino)methyl)thiazole-4-carboxamido)-2-methylpropanoic acid (1.26 g, 3.67 mmole) in 10 mL Dimethylformamide was added HBTU(O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate) (1.67 g, 4.40 mmole) and diisopropylethylamine (2.0 mL, 11.0 mmole). The resulting reaction mixture was stirred at room temperature for 10 minutes. (5)-tert-butyl 3-((S)-2-amino-3-methylbutanoyloxy)pent-4-enoate (1.0 g, 3.67 mmole) was added, and the resulting mixture was stirred overnight. Water and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc, the combined organic layer was dried over Na2SO4 and concentrated. It was purified by column chromatography, eluted with 1:1 Hex/EtOAc to get the desired product (2.1 g, 96% yield).

Workup

  1. customThe resulting reaction mixture
  2. stirringthe resulting mixture was stirred overnight
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc
  5. dry with materialthe combined organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customIt was purified by column chromatography
  8. washeluted with 1:1 Hex/EtOAc

Sources & evidence

ORD record
ord-ada3e7d5e2d14864896057bcb97ecd20
Source dataset
uspto-grants-2016_08
Patent number
US09422340B2

Reaction notes

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