Acetamide → 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

HRID 1096326Notes

Reaction equation

HRID 1096326 reaction equation
C1C[O:4]CC1.[CH3:6][C:7]([CH3:40])([CH2:10][C@@:11]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:16][C:15](=[O:17])[N:14]([C@H:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29](=[O:32])[N:28]([CH3:33])[CH:27]=3)=[CH:22][CH:21]=2)[CH3:19])[CH2:13][CH2:12]1)[C:8]#[N:9].C(N)(=O)C>Cl[Pd]Cl.O>[CH3:40][C:7]([CH3:6])([CH2:10][C@@:11]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:16][C:15](=[O:17])[N:14]([C@H:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29](=[O:32])[N:28]([CH3:33])[CH:27]=3)=[CH:22][CH:21]=2)[CH3:19])[CH2:13][CH2:12]1)[C:8]([NH2:9])=[O:4]

Participants

6

Reactant 3

HCID 178AcetamideHCID 8028TetrahydrofuranHCID 596356402,2-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)propanenitrile

Product 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

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent

Procedure

A THF:H2O (2 mL, 3:1) solution of 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)propanenitrile (55 mg, 0.12 mmol), acetamide (177 mg, 3 mmol) and PdCl2 (21 mg, 0.12 mmol) was stirred overnight. The solvent was removed and the crude material redissolved in CH3CN. The crude product was purified via prep HPLC to afford 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 (28 mg). LC-MS Method 1 tR=1.25 min, m/z=488 (M+1); 1H NMR (CDCl3) 7.55 (dd, 1H, J=9 Hz, 3 Hz), 7.42 (d, 1H, J=3 Hz), 7.32 (d, 1H, J=4 Hz), 7.29 (m, 4H), 7.14 (d, 2H, 8 Hz), 7.00 (d, 2H, J=8 Hz), 6.79 (d, 1H, J=9 Hz), 5.66 (q, 1H, J=8 Hz), 3.62 (s, 3H), 2.95-2.89 (m, 1H), 2.5 (d, 1H, J=15 Hz), 2.26-2.1 (m, 3H), 2.2 (d, 1H, J=15 Hz), 2.5 (d, 1H, J=15 Hz), 2.26-2.10 (m, 3H), 2.2 (d, 1H, J=15 Hz), 1.53 (d, 3H, J=7 Hz), 1.22 (s, 3H), 1.20 (s, 3H)

Workup

  1. customThe solvent was removed
  2. dissolutionthe crude material redissolved in CH3CN
  3. customThe crude product was purified via prep HPLC

Sources & evidence

ORD record
ord-47b4d741475c4fd989a9c72e56132094
Source dataset
uspto-grants-2012_03
Patent number
US08138178B2

Reaction notes

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