Acetic Acid → HCID 66594443, compound

HRID 1622934Notes

Reaction equation

HRID 1622934 reaction equation
[NH2:1][C@H:2]([CH3:9])[CH2:3][CH2:4][NH:5][CH:6]([CH3:8])[CH3:7].FC1C=CC(CNC(C2C(=O)C(O)=C3C(=O)N4[C@H](C)CCN(C(C)C)[C@H]4CN3C=2)=O)=CC=1.C[O:43][C:44]([C:46]1[N:47]([CH2:72][CH:73]=O)[CH:48]=[C:49]([C:61](=[O:71])[NH:62][CH2:63][C:64]2[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=2)[C:50](=[O:60])[C:51]=1[O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=O.C(O)(=O)C>ClCCl>[F:70][C:67]1[CH:66]=[CH:65][C:64]([CH2:63][NH:62][C:61]([C:49]2[C:50](=[O:60])[C:51]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[C:46]3[C:44](=[O:43])[N:1]4[C@H:2]([CH3:9])[CH2:3][CH2:4][N:5]([CH:6]([CH3:8])[CH3:7])[C@H:73]4[CH2:72][N:47]3[CH:48]=2)=[O:71])=[CH:69][CH:68]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 54713689HCID 54713689, compoundHCID 55285922HCID 55285922, compound2×HCID 596005723-Benzyloxy-5-(4-fluoro-benzylcarbamoyl)-4-oxo-1-(2-oxo-ethyl)-1,4-dihydro-pyridine-2-carboxylic acid methyl ester

Product 1

HCID 66594443HCID 66594443, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[(3R)-3-Aminobutyl](1-methylethyl)amine. The free diamine was prepared in a similar manlier as described in example Z-29. 1H NMR (400 MHz, CDCl3) δ 1.04 (d, J=6.4 Hz, 6H), 1.06 (d, J=6.4Hz, 3H), 1.41-1.58 (m, 5H), 2.62-2.66 (m, 2H), 2.74-2.80 (m, 1H), 2.92-3.00 (m, 1H). b) (4R,12aR)—N-[(4-Fluorophenyl)methyl]-7-hydroxy-4-methyl-1-(1-methylethyl)-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. 16 (40 mg, 0.088 mmol) and [(3R)-3-aminobutyl](1-methylethyl)amine (78 mg, 0.60 mmol) were reacted in dichloromethane (2 mL) with acetic acid to give (4R,12aR)—N-[(4-fluorophenyl)methyl]-4-methyl-1-(1-methylethyl)-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 (26 mg, 56%). This material was hydrogenated in a second step as described in example Z-2 to give (4R,12aR)—N-[(4-fluorophenyl)methyl]-7-hydroxy-4-methyl-1-(1-methylethyl)-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydropyrido[1′,2′:4,5]pyrazino[1,2-a]pyrimidine-9-carboxamide (21 mg, 90%) as an off-white solid. 1H NMR (4.00 MHz, CDCl3) δ 1.01 (d, J=5.6 Hz, 3H), 1.06 (d, J=6.0 Hz, 3H), 1.31 (d, J=6.8 Hz, 3H), 1.57 (m, 1H), 1.98 (m, 1H), 2.70-2.82 (m, 2H), 3.15 (m, 1H), 4.15-4.19 (m, 1H), 430 (m, 1H), 4.4.8 (s, 1H), 4.54-4.59 (m, 2H), 4.97 (m, 1H), 6.98 (m, 2H), 7.29-7.32 (m, 2H), 8.27 (s, 1H), 10.49 (s, 1H), 12.52 (s, 1H).

Sources & evidence

ORD record
ord-83bc5b21ac524804b8b161b8bc6ca7f7
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

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