HCID 66594381, compound → HCID 76182080, compound

HRID 920696Notes

Reaction equation

HRID 920696 reaction equation
Cl.N[C@H]1CCCC[C@H]1CNCCO.[F:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[CH2:22][NH:23][C:24]([C:26]1[C:27](=[O:56])[C:28]([O:48]CC2C=CC=CC=2)=[C:29]2[C:45](=[O:46])[N:33]3[CH:34]4[CH:39]([CH2:40][N:41]([CH2:42][CH2:43][OH:44])[CH:32]3[CH2:31][N:30]2[CH:47]=1)[CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:25]>>[F:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[CH2:22][NH:23][C:24]([C:26]1[C:27](=[O:56])[C:28]([OH:48])=[C:29]2[C:45](=[O:46])[N:33]3[CH:34]4[CH:39]([CH2:40][N:41]([CH2:42][CH2:43][OH:44])[CH:32]3[CH2:31][N:30]2[CH:47]=1)[CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:25]

Participants

3

Reactant 2

HCID 66594381HCID 66594381, compoundHCID 77150746HCID 77150746, compound

Product 1

HCID 76182080HCID 76182080, compound

Procedure

In a manner similar to that described in example Z-35, from 16a (45 mg, 0.0957 mmol) and racemic-2-({[(1S,2S)-2-aminocyclohexyl]methyl}amino)ethanol hydrochloride (102 mg, 0.418 mmol) was prepared racemic-(4aS,6aS,14aS)-N-[(2,4-difluorophenyl)methyl]-6-(2-hydroxyethyl)-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 (7 mg, 12%) as a white solid after silica gel chromatography (1.12% methanol/dichloromethane gradient elution). This material was deprotected in a second step similar to the procedure described in example Z-37. Thus, from racemic-(4aS,6aS,14aS)-N-[(2,4-difluorophenyl)methyl]-6-(2-hydroxyethy)-11,13-dioxo-12-[(phenylmethyl)oxy]-1,2,3,4,4a,5,8,8a,7,11,13,14a-dodecahydropyrido[1′,2′:4,5]pyrazino[1,2-a]quinazoline-10-carboxamide (7 mg, 0.0118 mmol) the title compound was prepared after purification by HPLC (3 mg, 50%). 1H NMR (CDCl3) 12.57 (br s, 1H), 10.45 (m, 1H), 8.29 (s, 1H), 7.34 (m, 1H), 6.78 (m, 2H), 4.80 (m, 1H), 4.71 (s, 1H), 4.62 (m, 2H), 4.44 (m, 1H), 4.33 (m, 1H), 3.75 (m, 1H), 3.62-3.20 (m, 3H), 3.13 (m, 1H), 2.74-2.71 (m, 2H), 2.24 (m, 1H), 1.90-137 (m, 12H), 1.27-1.23 (m, 3H) 1.12 (m, 1H); ES+MS: 503 (M+1).

Workup

  1. washafter silica gel chromatography (1.12% methanol/dichloromethane gradient elution)
  2. customafter purification by HPLC (3 mg, 50%)

Sources & evidence

ORD record
ord-bcce129a82634fd6867a339d2affd7e7
Source dataset
uspto-grants-2016_03
Patent number
US09273065B2

Reaction notes

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