HCID 66594464, compound → HCID 76182147, compound

HRID 1091602Notes

Reaction equation

HRID 1091602 reaction equation
Cl.N[C@H]1CCCC[C@H]1CNCCN1CCOCC1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[CH2:27][NH:28][C:29]([C:31]1[C:32](=[O:66])[C:33]([O:58]CC2C=CC=CC=2)=[C:34]2[C:55](=[O:56])[N:38]3[CH:39]4[CH:44]([CH2:45][N:46]([CH2:47][CH2:48][N:49]5[CH2:54][CH2:53][O:52][CH2:51][CH2:50]5)[CH:37]3[CH2:36][N:35]2[CH:57]=1)[CH2:43][CH2:42][CH2:41][CH2:40]4)=[O:30]>[Pd]>[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[CH2:27][NH:28][C:29]([C:31]1[C:32](=[O:66])[C:33]([OH:58])=[C:34]2[C:55](=[O:56])[N:38]3[CH:39]4[CH:44]([CH2:45][N:46]([CH2:47][CH2:48][N:49]5[CH2:50][CH2:51][O:52][CH2:53][CH2:54]5)[CH:37]3[CH2:36][N:35]2[CH:57]=1)[CH2:43][CH2:42][CH2:41][CH2:40]4)=[O:30]

Participants

4

Reactant 2

HCID 66594464HCID 66594464, compoundHCID 77150677HCID 77150677, compound

Product 1

HCID 76182147HCID 76182147, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

racemic-4aS,6aS,14aS)—N-[(2,4-Difluorophenyl)methyl]-12-hydroxy-6-[2-(4-morpholinyl)ethyl]-11,13-dioxo-1,2,3,4,4a5,6,6a,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-{[(1S,2S)-2-aminocyclohexyl]methyl}[2-(4-morpholinyl)ethyl]amine hydrochloride (95 mg, 0.272 mmol) and 16a (45 mg, 0.0957 mmol) was prepared racemic-(4aS,6aS,14aS)—N-[(2,4-difluorophenyl)methyl]-6-[2-(4-morpholinyl)ethyl]-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 (27 mg, 43%). This material was deprotected in a second step similar to the procedure described in example Z-37. From racemic-(4aS,6aS,14aS)—N-[(2,4-difluorophenyl)methyl]-6-[2-(4-morpholinyl)ethyl]-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]quinazolino-10-carboxamide (27 mg, 0.0408 mmol) and 10% Pd/C (1 mg) the title compound was prepared as a white solid after purification by HPLC. 1H NMR (CDCl3) 12.30 (br s, <1H), 10.41 (br s, 1H), 8.29 (s, 1H), 7.34 (m, 2H), 6.78 (m, 2H), 4.76 (m, 1H), 4.62-4.54 (m, 3H), 4.29 (m, 2H), 3.65 (m, 4H), 3.01 (m, 1H), 2.76 (m, 2H), 2.58-2.42 (m, 7H), 2.21 (m, 1H), 1.89-1.23 (m, 8H); ES+ MS: 572 (M+1).

Workup

  1. customafter purification by HPLC

Sources & evidence

ORD record
ord-2a54724f7443434ebed5bb4f77816891
Source dataset
uspto-grants-2012_03
Patent number
US08129385B2

Reaction notes

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