Acetic Acid → HCID 66594690, compound

HRID 1622959Notes

Reaction equation

HRID 1622959 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]([CH2:43][CH2:44][CH2:45]C)[CH2:36][CH2:37][NH:38][CH2:39][CH:40]([CH3:42])[CH3:41].[C:47](O)(=O)C>ClCCl>[F:29][C:26]1[CH:27]=[CH:28][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:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[C:5]3[C:3](=[O:2])[N:34]4[C@@H:35]([CH2:43][CH:44]([CH3:45])[CH3:47])[CH2:36][CH2:37][N:38]([CH2:39][CH:40]([CH3:41])[CH3:42])[C@@H:32]4[CH2:31][N:6]3[CH:7]=2)=[O:30])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 596005723-Benzyloxy-5-(4-fluoro-benzylcarbamoyl)-4-oxo-1-(2-oxo-ethyl)-1,4-dihydro-pyridine-2-carboxylic acid methyl esterHCID 86689374HCID 86689374, compound

Product 1

HCID 66594690HCID 66594690, compoundYield 25%

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 (25 mg, 0.055 mmol) and free based. [(3S)-3-amino-6-methylhexyl](2-methylpropyl)amine (21 mg, 0.11 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4S,12aS)—N-[(4-fluorophenyl)methyl]1,4-bis(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 (8 mg, 25%) as a film. This material was hydrogenated in a second step as described in example Z-2 to give (4S,12aS)—N-[(4-fluorophenyl)methyl]-7-hydroxy-1,4-bis(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 mg, 78%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 0.74 (d, J=6.4 Hz, 3H), 0.84 (d, J=6.4 Hz, 3H), 0.97-1.00 (m, 6H), 1.37-1.66 (m, 5H), 1.76-1.82 (m, 1H), 2.05-2.09 (m, 2H), 2.21-2.26 (m, 1H), 2.72-2.79 (m, 1H), 2.87-2.93 (m, 1H), 4.16-4.26 (m, 2H), 4.38 (m, 1H), 4.55-4.66 (m, 2H), 4.93-4.99 (m, 1H), 6.97-7.02 (m, 2H), 7.31-7.34 (m, 2H), 8.27 (s, 1H), 10.49 (m, 1H), 12.61 (s, 1H); ES+ MS: 499 (M+1).

Sources & evidence

ORD record
ord-c039764f064f464485b9be491eb19cc7
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

Loading…