(S)-6-(2-amino-2-methylpropyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one → methyl 2-methyl-1-((S)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propan-2-ylcarbamate

HRID 1187809Notes

Reaction equation

HRID 1187809 reaction equation
[NH2:1][C:2]([CH3:34])([CH3:33])[CH2:3][C@@:4]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:26])[CH:20]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1>CN(C1C=CN=CC=1)C.CCN(C(C)C)C(C)C.ClC(OC)=O.C(Cl)Cl>[CH3:34][C:2]([NH:1][C:8](=[O:10])[O:9][CH3:4])([CH3:33])[CH2:3][C@@:4]1([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:26])[CH:20]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1

Participants

6

Reactant 1

HCID 59635681(S)-6-(2-amino-2-methylpropyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

Product 1

HCID 59635641methyl 2-methyl-1-((S)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propan-2-ylcarbamateYield 110.8%

Reagents, catalysts & solvents 4

HCID 6586Methyl chloroformateCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 81531DiisopropylethylamineCatalystHCID 6344DichloromethaneSolvent

Procedure

A CH2Cl2 (1 mL) solution of (S)-6-(2-amino-2-methylpropyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (5 mg, 0.009 mmol) was treated with DMAP (5 mg, 0.04 mmol), i-Pr2NEt (10 drops), and methyl chloroformate (20 drops). The reaction was stirred overnight. The reaction solution was by prep HPLC affording methyl 2-methyl-1-((S)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propan-2-ylcarbamate (2.58 mg). LC-MS Method 1 tR=1.45 min, m/z=518 (M+1); 1H NMR (CDCl3) 7.66 (dd, 1H, J=9Hz, 2Hz), 7.48 (d, 1H, J=3Hz), 7.35-7.27 (m, 5H), 7.15 (d, 2H, J=8Hz), 7.01 (d, 2H, J=8Hz), 6.87 (d, 1H, J=9Hz), 5.67 (q, 1H, J=7Hz), 3.69 (s, 3H), 2.2 (s, 3H), 1.54 (d, 3H, J=7Hz), 1.46-1.36 (m, 2H), 1.30 (s, 3H), 1.20 (s, 3H).

Sources & evidence

ORD record
ord-4644d84868b64b5b8bb747c913c7df17
Source dataset
uspto-grants-2014_03
Patent number
US08673899B2

Reaction notes

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