Acetic Acid → HCID 66594692, compound

HRID 1622957Notes

Reaction equation

HRID 1622957 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([C:13]1[C:14](=[O:31])[C:15]([OH:30])=[C:16]2[C:27](=[O:28])[N:20]3[C@@H:21]([CH3:26])[CH2:22][CH2:23][N:24]([CH3:25])[C@@H:19]3[CH2:18][N:17]2[CH:29]=1)=[O:12].N[C@@H:33]([CH3:38])[CH2:34][CH2:35]NC.[C:39]([OH:42])(=O)[CH3:40].[Cl:43][CH2:44]Cl>>[ClH:43].[ClH:43].[NH2:20][C@@H:21]([CH3:26])[CH2:22][CH2:23][NH:24][CH3:19].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([C:13]1[C:14](=[O:31])[C:15]([OH:30])=[C:16]2[C:27](=[O:28])[N:20]3[C@@H:21]([CH3:26])[CH2:22][CH2:23][N:24]([CH3:25])[C@@H:19]3[CH2:18][N:17]2[CH:29]=1)=[O:12].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([C:13]1[C:14](=[O:31])[C:15]([O:42][CH2:39][C:40]2[CH:44]=[CH:35][CH:34]=[CH:33][CH:38]=2)=[C:16]2[C:27](=[O:28])[N:20]3[C@@H:21]([CH3:26])[CH2:22][CH2:23][N:24]([CH3:25])[C@@H:19]3[CH2:18][N:17]2[CH:29]=1)=[O:12]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 54713628HCID 54713628, compoundHCID 58015334HCID 58015334, compound

Product 3

HCID 54713628HCID 54713628, compoundHCID 66594692HCID 66594692, compoundYield 89%HCID 866372521309562-91-1

Procedure

[(3S)-3-Aminobutyl]methylamine dihydrochloride was prepared in a similar manner as described in example Z-47. 1H NMR (400 MHz, CDCl3) δ 1.18 (d, J=6.8 Hz, 3H), 1.82-1.91 (m, 1H), 1.94-2.03 (m, 1H), 2.53 (s, 3H), 2.89-2.93 (m, 2H), 3.22-3.30 (m, 1H), 8.02 (br, <1H), 8.81 (br, <1H). b) (4S,12aS)—N-[(2,4-Difluorophenyl)methyl]-7-hydroxy-1,4-dimethyl-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide. The title compound was made in two steps using a similar process to that described in example Z-2, 16a (4.0 mg, 0.085 mmol) and free based [(3S)-3-aminobutyl]methylamine (24 mg, 0.23 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-1,4-dimethyl-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 (39 mg, 89%) as a film. This material was hydrogenated in a second step as described in example 22 to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-7-hydroxy-1,4-dimethyl-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (32 mg, 97%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 1.33 (d, J=6.4 Hz, 3H), 1.46-1.50 (m, 1H), 2.12-2.14 (m, 1H), 2.32 (s, 3H), 2.83 (m, 2H), 4.24 (m, 3H), 4.62 (m, 2H), 5.02 (m, 1H), 6.77-6.79 (m, 2H), 7.33 (m, 1H), 8.30 (s, 1H), 10.43 (s, 1H), 12.50 (br, 1H); ES+ MS: 4.33 (M+1),

Sources & evidence

ORD record
ord-cfd2b9f190194c3e804c3f5090e55b62
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

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