HCID 77150793, compound → HCID 76182081, compound

HRID 1622950Notes

Reaction equation

HRID 1622950 reaction equation
Cl.C1(NCC2CCCCC2N)CC1.[CH:14]1([N:17]2[CH2:26][CH:25]3[CH:20]([CH2:21][CH2:22][CH2:23][CH2:24]3)[N:19]3[C:27](=[O:56])[C:28]4[N:29]([CH:31]=[C:32]([C:44]([NH:46][CH2:47][C:48]5[CH:53]=[CH:52][C:51]([F:54])=[CH:50][C:49]=5[F:55])=[O:45])[C:33](=[O:43])[C:34]=4[O:35]CC4C=CC=CC=4)[CH2:30][CH:18]23)[CH2:16][CH2:15]1>>[CH:14]1([N:17]2[CH2:26][CH:25]3[CH:20]([CH2:21][CH2:22][CH2:23][CH2:24]3)[N:19]3[C:27](=[O:56])[C:28]4[N:29]([CH:31]=[C:32]([C:44]([NH:46][CH2:47][C:48]5[CH:53]=[CH:52][C:51]([F:54])=[CH:50][C:49]=5[F:55])=[O:45])[C:33](=[O:43])[C:34]=4[OH:35])[CH2:30][CH:18]23)[CH2:16][CH2:15]1

Participants

3

Reactant 2

HCID 77150793HCID 77150793, compoundHCID 77150825HCID 77150825, compound

Product 1

HCID 76182081HCID 76182081, compound

Procedure

In a manner similar to that described in example Z-35, from 16a (45 mg, 0.0957 mmol) and racemic-(1S,2S)-2-[(cyclopropylamino)methyl]cyclohexanamine hydrochloride (102 mg, 0.425 mmol) was prepared racemic-(4aS,6aS,14aS)-6-cyclopropyl-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[1,2a]quinazoline-10-carboxamide 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)-6-cyclopropyl-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 (56 mg, 0.0949 mmol) the title compound was prepared as a white solid (41 mg, 81%). 1H NMR (CDCl3) 12.10 (br s, <1H), 10.45 (m, 1H), 8.27 (s, 1H), 7.33 (m, 1H), 6.88 (m, 2H), 477 (m, 1H), 4.61-4.49 (m, 4H), 4.33 (m, 1H), 2.94 (m, 1H), 2.79 (m, 1H), 2.17 (m, 1H), 1.86-0.86 (m, 10H), 0.658 (m, 1H), 0.499-0.32 (m, 2H); ES+ MS: 499 (M+1),

Workup

  1. washafter silica gel chromatography (1-12% methanol/dichloromethane gradient elution)

Sources & evidence

ORD record
ord-10fadf757d8142bfb1e78d5e9f9df9e8
Source dataset
uspto-grants-2014_07
Patent number
US08778943B2

Reaction notes

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