HCID 77150733, compound → HCID 76182073, compound

HRID 920695Notes

Reaction equation

HRID 920695 reaction equation
[C:1]([NH:4][CH2:5][CH2:6][N:7]1[CH2:16][CH:15]2[CH:10]([CH2:11][CH2:12][CH2:13][CH2:14]2)[N:9]2[C:17](=[O:46])[C:18]3[N:19]([CH:21]=[C:22]([C:34]([NH:36][CH2:37][C:38]4[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=4[F:45])=[O:35])[C:23](=[O:33])[C:24]=3[O:25]CC3C=CC=CC=3)[CH2:20][CH:8]12)(=[O:3])[CH3:2]>[Pd]>[C:1]([NH:4][CH2:5][CH2:6][N:7]1[CH2:16][CH:15]2[CH:10]([CH2:11][CH2:12][CH2:13][CH2:14]2)[N:9]2[C:17](=[O:46])[C:18]3[N:19]([CH:21]=[C:22]([C:34]([NH:36][CH2:37][C:38]4[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=4[F:45])=[O:35])[C:23](=[O:33])[C:24]=3[OH:25])[CH2:20][CH:8]12)(=[O:3])[CH3:2]

Participants

3

Reactant 1

HCID 77150733HCID 77150733, compound

Product 1

HCID 76182073HCID 76182073, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

racemic-4aS,6aS,14aS)-6-[2-(Acetylamino)ethyl]-N-[(2,4-difluorophenyl)methyl]-12-hydroxy-11,13-dioxo-1,2,3,4,4a,5,6,6a,7,11,13,14a-dodecahydropyrido[1′,2′:4,5]pyrazino[1,2-a]quinazoline-10-carboxamide. In a manner similar to that described in example Z-35, from racemic-N-[2-({[(1S,2S)-2-aminocyclohexyl]methyl}amino)ethyl]acetamide hydrochloride (82 mg, 0.849 mmol) and 16a (50 mg, 0.106 mmol) was prepared the title compound (24 mg, 86%). This material was deprotected in a second step similar to the procedure described in example Z-37. Thus, from racemic (4aS,6aS,14aS)-6-[2-(acetylamino)ethyl]-N-[(2,4-difluorophenyl)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 (24 mg, 0.0379 mmol) and 10% Pd/C (1 mg) was prepared the title compound as a white solid after purification by HPLC. 1H NMR (CDCl3) 12.50 (s, 1H), 10.44 (s, 1H), 8.35 (s, 1H), 7.32 (m, 1H), 6.79 (m, 2H), 5.86 (s, 1H), 4.78 (m, 1H), 4.61-4.50 (m, 3H), 4.30 (m, 1H), 8.35 (m, 1H), 3.18 (m, 1H), 2.96 (m, 1H), 2.76 (m, 2H), 2.48 (m, 1H), 2.19 (m, 1H), 1.89-1.28 (m, 12H): ES+MS: 544 (M+1).

Sources & evidence

ORD record
ord-8ff52d2fbdaf421ca1a4517988067537
Source dataset
uspto-grants-2016_03
Patent number
US09273065B2

Reaction notes

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