Potassium Phosphate, Tribasic → HCID 67385389, compound

HRID 912152Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:17][O:18][C:19]1[CH:56]=[CH:55][C:22]([CH2:23][N:24]([CH2:46][C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[C:25]2[N:30]=[CH:29][C:28]([C:31]3[C:32]4[CH2:45][CH2:44][NH:43][C:33]=4[N:34]=[C:35]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[N:36]=3)=[CH:27][N:26]=2)=[CH:21][CH:20]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl.CN(C)C=O>[CH3:54][O:53][C:50]1[CH:49]=[CH:48][C:47]([CH2:46][N:24]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([O:18][CH3:17])=[CH:56][CH:55]=2)[C:25]2[N:26]=[CH:27][C:28]([C:31]3[C:32]4[CH2:45][CH2:44][N:43]([C:2]5[CH:3]=[C:4]([C:9]([N:11]6[CH2:16][CH2:15][O:14][CH2:13][CH2:12]6)=[O:10])[CH:5]=[CH:6][C:7]=5[F:8])[C:33]=4[N:34]=[C:35]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[N:36]=3)=[CH:29][N:30]=2)=[CH:52][CH:51]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A dimethylformamide solution (2 ml) of the obtained (3-bromo-4-fluoro-phenyl)-morpholin-4-yl-methanone crude product (56.1 mg), bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (70.0 mg, 0.130 mmol), palladium acetate (2.9 mg, 0.013 mmol), X-Phos (12.4 mg, 0.0261 mmol) and potassium phosphate (55.1 mg, 0.260 mmol) was degassed under ultrasonic irradiation, followed by stirring at 100° C. for 6 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, followed by dilution with dichloromethane (10 ml), which was washed with saturated aqueous sodium chloride solution (10 ml). The organic layer was dried over sodium sulfate, followed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane/methanol=50/1), to obtain [3-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-4-fluoro-phenyl]-morpholin-4-yl-methanone as a pale brown solid (90.0 mg, 93%).

Workup

temperatureThe reaction mixture was cooled to room temperature
washwas washed with saturated aqueous sodium chloride solution (10 ml)
dry with materialThe organic layer was dried over sodium sulfate
concentrationfollowed by concentration under reduced pressure
customthe residue was purified by silica gel column chromatography (dichloromethane/methanol=50/1)

Sources & evidence

ORD record: ord-a889450fecaa47d39e99d531713cf466
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022205B2

Reaction notes

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