Diisopropylethylamine → (S)-2-((S)-2-{(S)-3-(4-Allyloxy-phenyl)-2-[(tert-butoxy-hydroxy-methyl)-amino]-propionylamino}-3-methyl-butyrylamino)-but-3-enoic acid methyl ester

HRID 2371335Notes

Reaction equation

HRID 2371335 reaction equation
[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:13]([NH:15][C@@H:16]([CH:20]([CH3:22])[CH3:21])[C:17](O)=[O:18])=[O:14])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].Cl.[CH3:32][O:33][C:34](=[O:39])[C@@H:35]([NH2:38])[CH:36]=[CH2:37].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>CN(C=O)C.CCOC(C)=O>[CH3:32][O:33][C:34](=[O:39])[C@@H:35]([NH:38][C:17](=[O:18])[C@@H:16]([NH:15][C:13](=[O:14])[C@@H:12]([NH:23][CH:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])[OH:25])[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[CH:6][CH:7]=1)[CH:20]([CH3:22])[CH3:21])[CH:36]=[CH2:37]

Participants

7

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 66847200(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acidHCID 86650247(S)-Methyl 2-aminobut-3-enoate hydrochloride

Product 1

HCID 66847466(S)-2-((S)-2-{(S)-3-(4-Allyloxy-phenyl)-2-[(tert-butoxy-hydroxy-methyl)-amino]-propionylamino}-3-methyl-butyrylamino)-but-3-enoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Acid 43 (1.03 g, 2.45 mmol), amine 63 (1.1 equiv) and HATU (1.1 equiv) were dissolved in anhydrous DMF (0.10-0.50M relative to acid). DIPEA was added (4 equiv) and the reaction mixture stirred at rt for 18 h. This was partitioned between EtOAc and 1M hydrochloric acid. The organic phase was washed sequentially with 1M hydrochloric acid and brine before being dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether to yield a white solid, 0.964 g, 76%. Rf=0.46 (1/1 EtOAc/(50/70) petroleum ether). m.p. 104-106° C.

Workup

  1. customThis was partitioned between EtOAc and 1M hydrochloric acid
  2. washThe organic phase was washed sequentially with 1M hydrochloric acid and brine
  3. dry with materialbefore being dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether
  7. customto yield a white solid, 0.964 g, 76%

Sources & evidence

ORD record
ord-67f1990d654241a1aae78a405ab818c7
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Reaction notes

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