HCID 66594381, compound → HCID 76182080, compound

HRID 1091605Notes

Reaction equation

HRID 1091605 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, compound2×

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]-1,2,3,4,4a,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-hydroxyethyl)-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 (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-0031fff08da84002b1211da271215243
Source dataset
uspto-grants-2012_03
Patent number
US08129385B2

Reaction notes

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