Acetic Acid → HCID 66594673, compound

HRID 1622939Notes

Reaction equation

HRID 1622939 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 54713702HCID 54713702, compoundHCID 86664872HCID 86664872, compound

Product 3

HCID 54713702HCID 54713702, compoundHCID 66594673HCID 66594673, compoundYield 90%HCID 86689373HCID 86689373, compound

Procedure

[(3R)-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 0.87 (d, J=5.2 Hz, 6H), 1.32 (m, 3H), 1.61 (m, 3H), 2.10-2.20 (m, 2H), 2.90-3.04 (m, 4H), 3.45 (m, 1H), 8.23 (br, <1H), 8.96 (br, <1H). b) (4R,12aR)—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 (40 mg, 0.085 mmol) and free [(3R)-3-aminobutyl](3-methylbutyl)amine (46 mg, 0.35 mmol) were reacted in dichloromethane (2 mid) with acetic acid to give (4R,12aR)—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 (44 mg, 90%) as a film. This material was hydrogenated in a second step as described in example Z-2 to give (4R,12aR)—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 (11 mg, 30%) as an off-white solid, 1H NMR (400 MHz, CDCl3) δ 0.84 (d, J=6.8 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 1.24-1.36 (m, 5H), 1.47-1.53 (m, 2H), 2.02-2.11 (m, 1H), 2.36-2.43 (m, 1H), 2.54-2.61 (m, 1H), 2.77-2.92 (m, 2H), 4.16-4.26 (m, 2H), 4.44 (m, 1H), 4.62-4.64 (m, 2H), 4.95-5.02 (m, 1H), 6.75-6.81 (m, 2H), 7.31-7.37 (m, 1H), 8.27 (s, 1H), 10.43 (m, 1H), 12.54 (s, 1H); ES+ MS: 489 (M+1),

Sources & evidence

ORD record
ord-0ba39636dcb24025bf0cc41abda00701
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

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