Acetic Acid → HCID 66594624, compound

HRID 1622935Notes

Reaction equation

HRID 1622935 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]([CH2:25][C:26]4[O:27][CH:28]=[CH:29][CH:30]=4)[C@@H:19]3[CH2:18][N:17]2[CH:34]=1)=[O:12].N[C@@H](C)CCN[CH2:42][C:43]1O[CH:45]=[CH:46][CH:47]=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][CH2:25][C:26]1[O:27][CH:28]=[CH:29][CH:30]=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]([CH2:25][C:26]4[O:27][CH:28]=[CH:29][CH:30]=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:45]=[CH:46][CH:47]=[CH:43][CH:42]=2)=[C:16]2[C:32](=[O:33])[N:20]3[C@@H:21]([CH3:31])[CH2:22][CH2:23][N:24]([CH2:25][C:26]4[O:27][CH:28]=[CH:29][CH:30]=4)[C@@H:19]3[CH2:18][N:17]2[CH:34]=1)=[O:12]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 54713692HCID 54713692, compoundHCID 66594455HCID 66594455, compound

Product 3

HCID 54713692HCID 54713692, compoundHCID 66594624HCID 66594624, compoundYield 70%HCID 86689372HCID 86689372, compound

Procedure

[(3S)-3-Aminobutyl](2-furanylmethyl)amine dihydrochloride was prepared in a similar manner as described in example Z-32, NMR (400 MHz, CDCl3/CD3OD) δ 1.27 (d, J=6.4 Hz, 3H), 1.96-2.05 (m, 1H), 2.1.4-2.19 (m, 1H), 3.00-3.04 (m, 2H), 3.38-3.39 (m, 1H), 4.11-4.18 (m, 2H), 6.34 (m, 1H), 6.59 (m, 1H), 7.40 (m, 1H), 8.18 (br, <1H), 9.41 (br, <1H), b) (4S,12aS)—N-[(2,4-Difluorophenyl)methyl]-1-(2-furanylmethyl)-7-hydroxy-4-methyl-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 (36 mg, 0.076 mmol) and free based [(3S)-3-aminobutyl](2-furanylmethyl)amine (70 mg, 0.42 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4S,12aS)—N-[(2,4-difluorophenyl)methyl]-1-(2-furanylmethyl)-4-methyl-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 (32 mg, 70%) 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]-1-(2-furanylmethyl)-7-hydroxy-4-methyl-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (20 mg, 76%), as an off-white solid, 1H NMR (400 MHz, CDCl3) δ 1.24 (d, J=6.8 Hz, 3H), 1.45-1.49 (m, 1H), 2,042.13 (m, 1H), 2.77-2.82 (m, 1H), 2.94-3.01 (m, 1H), 3.65 (d, J=15.6 Hz, 1H), 3.89 (d, J=16.0 Hz, 1H), 4.27-4.31 (m, 1H), 4.39-4.41 (m, 1H), 4:49-4.53 (m, 1H), 4.58-4.66 (m, 1H), 4.98-5.03 (m, 1H), 6.24 (m, 1H), 6.36 (m, 1H), 6.75-6.82 (m, 2H), 7.31-7.39 (m, 1H), 7.40 (m, 1H), 8.26 (s, 1H), 10.47 (m, 1H), 12.50 (br, 1H); ES+ MS: 499 (M+1).

Sources & evidence

ORD record
ord-c1ae6b53db9e4e71bcf206dd736499ac
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

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