Acetic Acid → HCID 66594545, compound

HRID 1622947Notes

Reaction equation

HRID 1622947 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:36])[C:15]([OH:35])=[C:16]2[C:32](=[O:33])[N:20]3[C@@H:21]([CH3:31])[CH2:22][CH2:23][N:24]([CH:25]4[CH2:30][CH2:29][S:28][CH2:27][CH2:26]4)[C@@H:19]3[CH2:18][N:17]2[CH:34]=1)=[O:12].N[C@@H](C)CCN[CH:42]1[CH2:47][CH2:46]S[CH2:44][CH2:43]1.[C:49]([OH:52])(=O)[CH3:50].[Cl:53]CCl>>[ClH:53].[ClH:53].[NH2:20][C@@H:21]([CH3:31])[CH2:22][CH2:23][NH:24][CH:25]1[CH2:30][CH2:29][S:28][CH2:27][CH2:26]1.[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:36])[C:15]([OH:35])=[C:16]2[C:32](=[O:33])[N:20]3[C@@H:21]([CH3:31])[CH2:22][CH2:23][N:24]([CH:25]4[CH2:30][CH2:29][S:28][CH2:27][CH2:26]4)[C@@H:19]3[CH2:18][N:17]2[CH:34]=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:36])[C:15]([O:52][CH2:49][C:50]2[CH:46]=[CH:47][CH:42]=[CH:43][CH:44]=2)=[C:16]2[C:32](=[O:33])[N:20]3[C@@H:21]([CH3:31])[CH2:22][CH2:23][N:24]([CH:25]4[CH2:26][CH2:27][S:28][CH2:29][CH2:30]4)[C@@H:19]3[CH2:18][N:17]2[CH:34]=1)=[O:12]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 54713617HCID 54713617, compoundHCID 66594522HCID 66594522, compound

Product 3

HCID 54713617HCID 54713617, compoundHCID 66594545HCID 66594545, compoundYield 54%HCID 86664879HCID 86664879, compound

Procedure

[(3S)-3-Aminobutyl]tetrahydro-2H-thiopyran-4-ylamine dihydrochloride was prepared in a similar manner as described in example Z-47. 1H NMR (400 MHz, CDCl3/CD3OD) δ 1.21 (d, J=6.4 Hz, 3H), 1.65-1.75 (m, 2H), 1.90-2.10 (m, 2H), 2.35 (m, 2H), 2.56-2.61 (m, 4H), 2.92-2.98 (m, 3H), 3,273.31 (m, 1H), 8.05 (br, <1H), 8.90 (br, <1H). b) (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-7-hydroxy-4-methyl-6,8-dioxo-1-(tetrahydro-2H-thiopyran-4-yl)-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 (80 mg, 0.17 mmol) and free based [(3S)-3-aminobutyl]tetrahydro-2H-thiopyran-4-ylamine (108 mg, 0.58 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-4-methyl-6,8-dioxo-7-[(phenylmethyl)oxy]-1-(tetrahydro-2H-thiopyran-4-yl)-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (56 mg, 54%) as a film. This material was debenzylated in a second step to in a manner similar to Z-26 to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-7-hydroxy-4-methyl-6,8-dioxo-1-(tetrahydro-2H-thiopyran-4-yl)-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (56 mg, >100%) as an off-white solid, 1H NMR (4.00 MHz, CDCl3) δ 1.30 (d, J=6.8 Hz, 3H), 1.54-1.58 (m, 1H), 1.72-1.82 (m, 3H), 1.97-2.11 (m, 2H), 2.60-2.76 (5H), 2.86 (m, 2H), 4.17-4.30 (m, 2H), 4.62-4.66 (m, 3H), 4.92-4.96 (m, 1H), 6.75-6.82 (m, 2H), 7.32-7.38 (m, 1H), 8.31 (s, 1H), 10.46 (s, 1H), 12.48 (s, 1H); ES+ MS: 519 (M+1).

Sources & evidence

ORD record
ord-90c7f86669a74238979e1c94379444a9
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

Loading…