HCID 66594505, compound → HCID 76182071, compound

HRID 920694Notes

Reaction equation

HRID 920694 reaction equation
Cl.N[C@H]1CCCC[C@H]1CNC.[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[CH2:20][NH:21][C:22]([C:24]1[C:25](=[O:52])[C:26]([O:44]CC2C=CC=CC=2)=[C:27]2[C:41](=[O:42])[N:31]3[CH:32]4[CH:37]([CH2:38][N:39]([CH3:40])[CH:30]3[CH2:29][N:28]2[CH:43]=1)[CH2:36][CH2:35][CH2:34][CH2:33]4)=[O:23]>[Pd]>[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[CH2:20][NH:21][C:22]([C:24]1[C:25](=[O:52])[C:26]([OH:44])=[C:27]2[C:41](=[O:42])[N:31]3[CH:32]4[CH:37]([CH2:38][N:39]([CH3:40])[CH:30]3[CH2:29][N:28]2[CH:43]=1)[CH2:36][CH2:35][CH2:34][CH2:33]4)=[O:23]

Participants

4

Reactant 2

HCID 66594505HCID 66594505, compoundHCID 77150780HCID 77150780, compound2×

Product 1

HCID 76182071HCID 76182071, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

In a manner similar to that described in example Z-35, from racemic-{[(1S,2S)-2-aminocyclohexyl]methyl}methylamine hydrochloride (46 mg, 0.215 mmol) and 16a (35 mg, 0.0744 mmol) was prepared racemic-(4aS,6aS,14aS)-N-[(2,4-difluorophenyl)methyl]-6-methyl-11,13-dioxo-12-[(phenylmethyl)oxy]-1,2,3,4,4a,5,6,6a,7,11,13,14a-dodecahydropyrido[1′,2′:4,5]pyrazino[1,2-a]quinazoline-10-carboxamide (17 mg, 41%) as a white solid. This material was deprotected in s second step similar to the procedure described in example Z-37. Thus, from racemic-(4aS,6aS,14aS)-N-[(2,4-difluorophenyl)methyl]-6-methyl-11,13-dioxo-12-[(phenylmethyl)oxy]-1,2,8,4,4a,5,6,6a,7,11,13,14a-dodecahydropyrido[1′,2′:4,5]pyrazino[1,2-a]quinazoline-10-carboxamide (17 mg, 0.0302 mmol) and 10% Pd/C (1 mg) was prepared the title compound as a white solid (9 mg, 64%). 1H NMR (CDCl3) 10.44 (m, 1H), 8.29 (s, 1H), 7.34 (m, 1H), 6.79 (m, 2H), 4.78 (m, 1H), 4.62 (br s, 2H), 4.20 (br s, 2H), 3.41 (s, 1H), 2.92 (m, 1H), 2.66 (m, 1H), 2.35-2.25 (m, 4H), 1.90-1.74 (m, 2H), 1.67-1.24 (m, 6H); ES+MS: 473 (M+1).

Sources & evidence

ORD record
ord-e47a09ec2fad40909ca9d8e51d3fa6ee
Source dataset
uspto-grants-2016_03
Patent number
US09273065B2

Reaction notes

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