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 2036392Notes

Reaction equation

HRID 2036392 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-8961fe96721349a99c25da8b477996a9
Source dataset
uspto-grants-2013_11
Patent number
US08575157B2

Reaction notes

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