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 1191740Notes

Reaction equation

HRID 1191740 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-8db5a6e4f8454a04ae7ef976c69c2af2
Source dataset
uspto-grants-2014_03
Patent number
US08680093B2

Reaction notes

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