Diisopropylethylamine → 4-[(4aR,7aR)-Octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-6-({4-[(3-amino-1,2-benz-isoxazol-4-yl)oxy]-3-fluorophenyl}amino)-2-pyrimidinylamine

HRID 16435

Reaction equation

[NH2:1][C:2]1[C:6]2[C:7]([O:11][C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19]4[CH:24]=[C:23](Cl)[N:22]=[C:21]([NH2:26])[N:20]=4)=[CH:14][C:13]=3[F:27])=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][N:3]=1.[NH:28]1[CH2:33][CH2:32][CH2:31][C@@H:30]2[CH2:34][NH:35][CH2:36][C@H:29]12.C(N(C(C)C)CC)(C)C>C(C(CCCC)CO)C>[NH:28]1[CH2:33][CH2:32][CH2:31][C@@H:30]2[CH2:34][N:35]([C:23]3[CH:24]=[C:19]([NH:18][C:15]4[CH:16]=[CH:17][C:12]([O:11][C:7]5[C:6]6[C:2]([NH2:1])=[N:3][O:4][C:5]=6[CH:10]=[CH:9][CH:8]=5)=[C:13]([F:27])[CH:14]=4)[N:20]=[C:21]([NH2:26])[N:22]=3)[CH2:36][C@H:29]12

Participants

Conditions

Temperature: 150 °C

Procedure

88 mg (0.23 mmol) of N-{4-[(3-amino-1,2-benzisoxazol-4-yl)oxy]-3-fluorophenyl}-N-(2-amino-6-chloro-4-pyrimidinyl)amine (from example 3) and 114.8 mg (0.91 mmol) of [(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridine together with 294.1 mg (2.28 mmol) of diisopropylethylamine are dissolved in 4 ml of 2-ethylhexanol, and the mixture is stirred at 150° C. for 3 h. After cooling, the reaction mixture is filtered and water is added. The mixture is extracted repeatedly with ethyl acetate, the organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC.

Workup

temperatureAfter cooling
filtrationthe reaction mixture is filtered
additionwater is added
extractionThe mixture is extracted repeatedly with ethyl acetate
dry with materialthe organic phase is dried over magnesium sulfate
customthe solvent is removed under reduced pressure
customThe residue is purified by preparative HPLC

Sources & evidence

ORD record: ord-30b698dcf3db4e6b9e7782296266353a
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737153B2

Linked notes

Loading…