4-Amino-6-benzyloxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline → 4-Amino-6-hydroxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline

HRID 2228491Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[C:9]([O:12]CC3C=CC=CC=3)[CH:10]=2)[N:5]=[C:4]([N:22]2[CH2:28][CH2:27][CH2:26][N:25]([C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[O:30])[CH2:24][CH2:23]2)[N:3]=1>[Pd].C(O)C>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[C:9]([OH:12])[CH:10]=2)[N:5]=[C:4]([N:22]2[CH2:28][CH2:27][CH2:26][N:25]([C:29]([N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)=[O:30])[CH2:24][CH2:23]2)[N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

10% palladium on charcoal (3 g) was added to a suspension of 4-amino-6-benzyloxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline (16.35 g, 0.033 mol) in ethanol (800 ml) and the reaction stirred at 50° C. under a hydrogen atmosphere of 414 kPa (60 p.s.i.) for 72 hours. On cooling, the reaction mixture was filtered through Arbocel™, washed well with further ethanol and the filtrate concentrated under reduced pressure. The crude product was purified on silica gel eluting with a solvent gradient of 0.880 aqueous ammonia:methanol:dichloromethane (0.5:3.5:96 to 1:7:92, v/v) to give the subtitle compound as a white solid (7.1 g, 53%). Rf 0.17 (0.880 aqueous ammonia:methanol:dichloromethane 1:7:92, v/v). MS m/z 403 (MH)+.

Workup

temperatureOn cooling
filtrationthe reaction mixture was filtered through Arbocel™
washwashed well with further ethanol
concentrationthe filtrate concentrated under reduced pressure
customThe crude product was purified on silica gel eluting with a solvent gradient of 0.880 aqueous ammonia:methanol:dichloromethane (0.5:3.5:96 to 1:7:92

Sources & evidence

ORD record: ord-1b7e884ce4c34ff5a14b92571c83b55d
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06417194B1

Reaction notes

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