Azepane → HCID 66584216, compound

HRID 500703Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:27][CH3:28])=[C:17]([NH:20][C:21](=[O:26])[CH:22]=[CH:23][CH2:24]Cl)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[NH:29]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:27][CH3:28])=[C:17]([NH:20][C:21](=[O:26])[CH:22]=[CH:23][CH2:24][N:29]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 70 °C

Procedure

300 g of 4-Chloro-but-2-enoic acid [4-(3-chloro4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide and 78 mg azepane were dissolved in 5 ml THF and purged with nitrogen. 0.25 ml DIEA was added and the mixture was stirred at 70° C. for 2 days. The mixture was then diluted with 20 ml ethyl acetate, washed with water and brine and dried over Na2SO4. The resulting solids were flash chromatographed with 0-4% methanol in chloroform. The product was dissolved in CH2Cl2 and treated with excess HCl and ether, then evaporated to dryness to give 115 mg of 4-Azepan-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide (33% yield).

Workup

custompurged with nitrogen
addition0.25 ml DIEA was added
additionThe mixture was then diluted with 20 ml ethyl acetate
washwashed with water and brine
dry with materialdried over Na2SO4
customchromatographed with 0-4% methanol in chloroform
dissolutionThe product was dissolved in CH2Cl2
additiontreated with excess HCl and ether
customevaporated to dryness

Sources & evidence

ORD record: ord-2cf940dfd3d249d5bcff349767dde995
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772243B2

Reaction notes

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