Water → 2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl 2,2-dimethylpropionate

HRID 1631164Notes

Reaction equation

[C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[NH2:8][C:9]1[N:18]=[C:17]([C:19]([N:21]2[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:30]3[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=3[CH2:38][OH:39])[CH:15]=2)[N:10]=1.C(OCC)(=O)C.O>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH3:3][C:2]([CH3:5])([CH3:4])[C:1]([O:39][CH2:38][C:31]1[CH:32]=[C:33]([F:37])[C:34]([F:36])=[CH:35][C:30]=1[C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([NH2:8])[N:18]=[C:17]2[C:19]([N:21]1[CH2:22][C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:29]1)=[O:20])=[O:6]

Participants

Conditions

Temperature: 80 °C

Procedure

47 μl of pivaloyl chloride are added to a solution of 200 mg of [2-amino-6-(4,5-difluoro-2-hydroxymethylphenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone and 2 mg of 4-(dimethylamino)pyridine (DMAP) in 4 ml of dimethylformamide, and the mixture is stirred at 80° C. for 16 h. 8 ml of ethyl acetate and 8 ml of water are added, the organic phase is separated off and evaporated to dryness in vacuo. The residue is dissolved in 1 ml of dimethyl sulfoxide and purified by chromatography (reversed phase HPLC).

Workup

customthe organic phase is separated off
customevaporated to dryness in vacuo
dissolutionThe residue is dissolved in 1 ml of dimethyl sulfoxide
custompurified by chromatography (reversed phase HPLC)

Sources & evidence

ORD record: ord-592c3d3d4cf6472ab893848fe720b6ac
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791129B2

Reaction notes

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