HCID 69292479, compound → HCID 76182081, compound

HRID 920697Notes

Reaction equation

HRID 920697 reaction equation
C1N2C3C(C=NC2=CN=C1)=CC=CC=3C(N)=O.Cl.C1(NCC2CCCCC2N)CC1.[CH:31]1([N:34]2[CH2:43][CH:42]3[CH:37]([CH2:38][CH2:39][CH2:40][CH2:41]3)[N:36]3[C:44](=[O:73])[C:45]4[N:46]([CH:48]=[C:49]([C:61]([NH:63][CH2:64][C:65]5[CH:70]=[CH:69][C:68]([F:71])=[CH:67][C:66]=5[F:72])=[O:62])[C:50](=[O:60])[C:51]=4[O:52]CC4C=CC=CC=4)[CH2:47][CH:35]23)[CH2:33][CH2:32]1>>[CH:31]1([N:34]2[CH2:43][CH:42]3[CH:37]([CH2:38][CH2:39][CH2:40][CH2:41]3)[N:36]3[C:44](=[O:73])[C:45]4[N:46]([CH:48]=[C:49]([C:61]([NH:63][CH2:64][C:65]5[CH:70]=[CH:69][C:68]([F:71])=[CH:67][C:66]=5[F:72])=[O:62])[C:50](=[O:60])[C:51]=4[OH:52])[CH2:47][CH:35]23)[CH2:33][CH2:32]1

Participants

4

Reactant 3

HCID 69292479HCID 69292479, compoundHCID 77150793HCID 77150793, compoundHCID 77150825HCID 77150825, compound2×

Product 1

HCID 76182081HCID 76182081, compound

Procedure

racemic-(4aS,6aS,14aS)-6-Cyclopropyl-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 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[1,2-a]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-87. 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), 4.77 (m, 1H), 4.61-4.40 (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-9bf02f973fca4a8f88b1358ad7a69e66
Source dataset
uspto-grants-2016_03
Patent number
US09273065B2

Reaction notes

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