Acetonitrile--water (1/1) → (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

HRID 470421Notes

Reaction equation

HRID 470421 reaction equation
C[C:2]([CH3:36])([CH2:6][C@@:7]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:12][C:11](=[O:13])[N:10]([C@H:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25](=[O:28])[N:24]([CH3:29])[CH:23]=3)=[CH:18][CH:17]=2)[CH3:15])[CH2:9][CH2:8]1)[C:3](N)=O.CC#[N:39].O>>[NH2:39][C:2]([CH3:36])([CH3:3])[CH2:6][C@@:7]1([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[O:12][C:11](=[O:13])[N:10]([C@H:14]([C:16]2[CH:17]=[CH:18][C:19]([C:22]3[CH:27]=[CH:26][C:25](=[O:28])[N:24]([CH3:29])[CH:23]=3)=[CH:20][CH:21]=2)[CH3:15])[CH2:9][CH2:8]1

Participants

3

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 596357972,2-dimethyl-3-((R)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propanamide

Product 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

Procedure

A foil covered flask charged with 2,2-dimethyl-3-((R)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propanamide (20 mg, 0.04 mmol) in 1:1 CH3CN/H2O (1 mL) was treated with PhI(O2CCF3)2 (31 mg, 0.07 mmol). The reaction was complete after 24 h. The solvent was removed and the crude material purified by prep HPLC to afford (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 (16 mg). LC/MS ES+=460 (M+1). LC-MS Method 1 tR=1.06 min, m/z=460 (M+1); 1H NMR (CDCl3) 7.60 (dd, 1H, J=9 Hz, 2 Hz), 7.46 (d, 1H, J=3 Hz), 7.39-7.27 (m, 5H), 7.20 (d, 2H, J=7 Hz), 7.1 (d, 2H, J=8 Hz), 6.78 (d, 1H, J=9 Hz, 5.61 (q, 1H, J=7 Hz), 3.65 (s, 3H), 2.87 (m, 1H), 2.80 (d, 1H, J=16 Hz), 2.23 (d, 1H, J=16 Hz), 2.19-2.08 (m, 3H), 1.54 (d, 3H, J=7 Hz), 1.41 (s, 3H), 0.96 (s, 3H).

Workup

  1. customThe solvent was removed
  2. customthe crude material purified by prep HPLC

Sources & evidence

ORD record
ord-031b5e807a50404499157b497f3ebe96
Source dataset
uspto-grants-2014_01
Patent number
US08629138B2

Reaction notes

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