Acetic Acid → HCID 66594490, compound

HRID 1622941Notes

Reaction equation

HRID 1622941 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:35])[C:15]([OH:34])=[C:16]2[C:31](=[O:32])[N:20]3[C@@H:21]([CH3:30])[CH2:22][CH2:23][N:24]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C@@H:19]3[CH2:18][N:17]2[CH:33]=1)=[O:12].N[C@@H](C)CCN[CH2:41][CH2:42][CH:43]([CH3:45])[CH3:44].[C:47](O)(=O)[CH3:48].[Cl:51]CCl>>[ClH:51].[ClH:51].[NH2:20][C@@H:21]([CH3:30])[CH2:22][CH2:23][NH:24][CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28].[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:35])[C:15]([OH:34])=[C:16]2[C:31](=[O:32])[N:20]3[C@@H:21]([CH3:30])[CH2:22][CH2:23][N:24]([CH2:25][CH2:26][CH:27]([CH3:28])[CH3:29])[C@@H:19]3[CH2:18][N:17]2[CH:33]=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:35])[C:15]([O:34][CH2:45][C:43]2[CH:42]=[CH:41][CH:48]=[CH:47][CH:44]=2)=[C:16]2[C:31](=[O:32])[N:20]3[C@@H:21]([CH3:30])[CH2:22][CH2:23][N:24]([CH2:25][CH2:26][CH:27]([CH3:28])[CH3:29])[C@@H:19]3[CH2:18][N:17]2[CH:33]=1)=[O:12]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 54713704HCID 54713704, compoundHCID 86664875HCID 86664875, compound

Product 3

HCID 54713704HCID 54713704, compoundHCID 66594490HCID 66594490, compoundYield 72%HCID 86664874HCID 86664874, compound

Procedure

[(3S)-3-Aminobutyl](3-methylbutyl)amine dihydrochloride was prepared in a similar manner as described in example Z-32, 1H NMR (400 MHz, CDCl3/CD3OD) δ 0.86 (d, J=5.6 Hz, 6H), 1.27 (d, J=6.0 Hz, 3H), 1.58 (m, 3H), 2.03-2.14 (m, 2H), 2.87-2.09 (m, 4H), 3.38 (m, 1H), 8.1.5 (br, <1H), 8.87 (br, <1H), b) (4S,12aS)—N-[(2,4-Difluorophenyl)methyl]-7-hydroxy-4-methyl-1-(3-methylbutyl)-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 (0.100 g, 0.21 mmol) and free based [(3S)-3-aminobutyl](3-methylbutyl)amine (0.104 g, 0.66 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-4-methyl-1-(3-methylbutyl)-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 (88 mg, 72%) as a film. This material was hydrogenated in a second step as described in example Z-2 to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-7-hydroxy-4-methyl-1-(3-methylbutyl)-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (55 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 0.84 (a, J=6.4 Hz, 3H), 0.85 (d, J=6.4 Hz, 3H), 1.24-1.37 (m, 5H), 1.45-1.53 (m, 2H), 2.02-2.11 (m, 1H), 2.37-2.44 (m, 1H), 2.56-2.63 (m, 1H), 2.80-2.92 (m, 2H), 4.22-4.29 (m, 2H), 4.45 (s, 1H), 4.62-4.63 (m, 2H), 4.97-5.00 (m, 1H), 6.75-6.82 (m, 2H), 7.31-7.37 (m, 1H), 8.37 (s, 1H), 10.48 (m, 1H), 12.53 (br, 1H); ES+ MS: 489 (M+1).

Sources & evidence

ORD record
ord-aca8c5ff171547c286c88107f2b00206
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

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