[2-Amino-6-(2-chloromethyl-4,5-difluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone → [2-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-4,5-difluorophenyl]methyl diethyl phosphate

HRID 1631184Notes

Reaction equation

[CH2:1]([O:3][P:4]([O-:9])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].C([N+](CCCC)(CCCC)CCCC)CCC.[NH2:27][C:28]1[N:37]=[C:36]([C:38]([N:40]2[CH2:48][C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[CH2:41]2)=[O:39])[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:49]3[CH:54]=[C:53]([F:55])[C:52]([F:56])=[CH:51][C:50]=3[CH2:57]Cl)[CH:34]=2)[N:29]=1>C(#N)C>[P:4]([O:6][CH2:7][CH3:8])([O:3][CH2:1][CH3:2])([O:9][CH2:57][C:50]1[CH:51]=[C:52]([F:56])[C:53]([F:55])=[CH:54][C:49]=1[C:33]1[CH:34]=[C:35]2[C:30](=[CH:31][CH:32]=1)[N:29]=[C:28]([NH2:27])[N:37]=[C:36]2[C:38]([N:40]1[CH2:41][C:42]2[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:48]1)=[O:39])=[O:5]

Participants

Conditions

Temperature: 80 °C

Procedure

800 mg of tetrabutylammonium diethylphosphate are added to 270 mg of [2-amino-6-(2-chloromethyl-4,5-difluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone dissolved in 20 ml of acetonitrile, and the solution obtained is heated at 80° C. for 2 h. After cooling to 25° C., undissolved material is filtered off, and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in 1 ml of dimethyl sulfoxide and purified by chromatography (reversed phase).

Workup

customthe solution obtained
temperatureAfter cooling to 25° C.
filtrationundissolved material is filtered off
customthe filtrate is evaporated to dryness in vacuo
dissolutionThe residue is dissolved in 1 ml of dimethyl sulfoxide
custompurified by chromatography (reversed phase)

Sources & evidence

ORD record: ord-7062dc1aa6d14263a2620f22244192ef
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791129B2

Reaction notes

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