Acetic Acid → (4R,12aR)-N-[(4-fluorophenyl)methyl]-4-methyl-1-(2 methylpropyl)-6,8-dioxo-7-[(phenylmethyl)oxy]-1,2,3,4,6,8,12,12a-octahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide

HRID 920690Notes

Reaction equation

HRID 920690 reaction equation
C[O:2][C:3]([C:5]1[N:6]([CH2:31][CH:32]=O)[CH:7]=[C:8]([C:20](=[O:30])[NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[C:9](=[O:19])[C:10]=1[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O.[NH2:34][C@H:35]([CH3:43])[CH2:36][CH2:37][NH:38][CH2:39][CH:40]([CH3:42])[CH3:41].C(O)(=O)C>ClCCl>[F:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][NH:21][C:20]([C:8]2[C:9](=[O:19])[C:10]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[C:5]3[C:3](=[O:2])[N:34]4[C@H:35]([CH3:43])[CH2:36][CH2:37][N:38]([CH2:39][CH:40]([CH3:42])[CH3:41])[C@H:32]4[CH2:31][N:6]3[CH:7]=2)=[O:30])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 55283812[(3R)-3-aminobutyl](2-methylpropyl)amineHCID 596005723-Benzyloxy-5-(4-fluoro-benzylcarbamoyl)-4-oxo-1-(2-oxo-ethyl)-1,4-dihydro-pyridine-2-carboxylic acid methyl ester

Product 1

HCID 66594495(4R,12aR)-N-[(4-fluorophenyl)methyl]-4-methyl-1-(2 methylpropyl)-6,8-dioxo-7-[(phenylmethyl)oxy]-1,2,3,4,6,8,12,12a-octahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrimidine-9-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was made in two steps using a similar process to that described in example Z-2. 16 (40 mg, 0.09 mmol) and [(3R)-3-aminobutyl](2-methylpropyl)amine (65 mg, 0.45 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4R,12aR)-N-[(4-fluorophenyl)methyl]-4-methyl-1-(2-methylpropyl)-6,8-dioxo-7-[(phenylmethyl)oxy]-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (29 mg, 60%). This material was hydrogenated in a second step as described in example Z-2 to give (4R,12aR)-N-[(4-fluorophenyl)methyl-7-hydroxy-4-methyl-1-(2-methylpropyl)-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydropyrido 1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (18 mg, 75%) as a tan solid. 1H NMR (400 MHz, CDCl3) δ 0.77 (d, J=6.4 Hz, 3H), 0.84 (d, J=6.4 Hz, 3H), 1.32 (d, J=7.2 Hz), 1.45-1.49 (m, 1H), 1.57-1.67 (m, 1H), 2.08-2.12 (m, 2H), 2.21-2.27 (m, 1H), 2.73-2.79 (m, 1H), 2.87-2.92 (m, 1H), 4.16-4.24 (m, 2H), 4.45 (s, 1H), 4.54-4.64 (m, 2H), 4.96-4.99 (m, 1H), 6.96-7.00 (m, 2H), 7.29-7.82 (m, 2H), 8.27 (s, 1H), 10.46 (s, 1H), 12.55 (s, 1H); ES+MS: 456 (M+1).

Sources & evidence

ORD record
ord-6338653269164e4384855d3d46def143
Source dataset
uspto-grants-2016_03
Patent number
US09273065B2

Reaction notes

Loading…