Monomethylamine methanol → 6-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl) ethyl)phenyl)-N-methylnicotinamide

HRID 2193471Notes

Reaction equation

HRID 2193471 reaction equation
[OH:1][C:2]([CH3:36])([CH3:35])[CH2:3][C@@:4]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=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:28]=[CH:27][C:22]([C:23](OC)=[O:24])=[CH:21][N:20]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.[NH2:37][CH3:38].CO>>[OH:1][C:2]([CH3:36])([CH3:35])[CH2:3][C@@:4]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH:28]=[CH:27][C:22]([C:23]([NH:37][CH3:38])=[O:24])=[CH:21][N:20]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1

Participants

3

Reactant 2

HCID 57454252Monomethylamine methanolHCID 59532382methyl 6-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)nicotinate

Product 1

HCID 446258446-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl) ethyl)phenyl)-N-methylnicotinamideYield 36%

Procedure

Methyl 6-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)nicotinate (150 mg, 0.307 mmol) was dissolved in NH2Me/MeOH (10 mL). The mixture was stirred at rt overnight. The solvent was removed in vacuo to give the crude product, which was purified by preparative HPLC and chiral HPLC to afford 6-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-N-methylnicotinamide (54 mg, 36%). LC-MS Method 2 tR=1.117 min, m/z=430.1; 1H NMR (CD3OD) 0.93 (s, 3H), 1.27 (s, 3H), 1.59 (d, 3H), 2.16 (s, 2H), 2.22-2.37 (m, 1H), 2.41-2.60 (m, 2H), 2.99 (s, 3H), 3.11 (m, 1H), 5.60 (m, 1H), 7.12 (d, 1H), 7.29 (m, 5H), 7.80 (m, 2H), 8.01 (d, 1H), 8.41 (d, 1H), 9.03 (s, 1H).

Workup

  1. customThe solvent was removed in vacuo
  2. customto give the crude product, which
  3. customwas purified by preparative HPLC and chiral HPLC

Sources & evidence

ORD record
ord-d40d44772c8846b899225962bf61e919
Source dataset
uspto-grants-2012_12
Patent number
US08329897B2

Reaction notes

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