Red-Al → (3-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl}-allyl)-carbamic acid tert-butyl ester

HRID 1783601Notes

Reaction equation

[C:1]([O:5][C:6](=[O:38])[NH:7][CH2:8][C:9]#[C:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)=[C:24]([Cl:37])[CH:23]=1)([CH3:4])([CH3:3])[CH3:2].COCCO[AlH2-]OCCOC.[Na+]>C1(C)C=CC=CC=1.C1COCC1>[C:1]([O:5][C:6](=[O:38])[NH:7][CH2:8][CH:9]=[CH:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)=[C:24]([Cl:37])[CH:23]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

(3-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl}-allyl)-carbamic acid tert-butyl ester is prepared by adding (3-{4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester (3.00 g, 5.63 mmol) to a mixture of Red-Al (5 ml of a 65% wt solution in toluene) in THF (50 ml) at 0° C. under N2. After stirring for 3 h at 0° C., the reaction mixture is quenched by the addition of 10 ml of 10% K2CO3 solution followed by water. The reaction mixture is extracted with ethyl acetate. The organic extracts are dried (Na2SO4), concentrated, and purified by column chromatography (EtOAc:Hex 1:1) to provide 2.01 g (67%) clean desired product.

Workup

customthe reaction mixture is quenched by the addition of 10 ml of 10% K2CO3 solution
extractionThe reaction mixture is extracted with ethyl acetate
dry with materialThe organic extracts are dried (Na2SO4)
concentrationconcentrated
custompurified by column chromatography (EtOAc:Hex 1:1)

Sources & evidence

ORD record: ord-2a498fed478945c6b1375adfee8581c0
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07501427B2

Reaction notes

Loading…