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

HRID 1631165Notes

Reaction equation

[C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].[NH2:7][C:8]1[N:17]=[C:16]([C:18]([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21]2)=[O:19])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:29]3[CH:34]=[C:33]([F:35])[C:32]([F:36])=[CH:31][C:30]=3[CH2:37][OH:38])[CH:14]=2)[N:9]=1.C(OCC)(=O)C.O>CN(C)C1C=CN=CC=1.CN(C)C=O>[C:1]([O:38][CH2:37][C:30]1[CH:31]=[C:32]([F:36])[C:33]([F:35])=[CH:34][C:29]=1[C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([NH2:7])[N:17]=[C:16]2[C:18]([N:20]1[CH2:21][C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:28]1)=[O:19])(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

40 μl of isobutyryl chloride are added to a solution of 150 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 5 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-224a421973ba4032a00667f2ff2aa72e
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791129B2

Reaction notes

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