Sodium Carbonate → (S)-1-methyl-3-(4-(4-(3-methylmorpholino)pyrimidin-2-yl)phenyl)urea

HRID 1771551Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[CH:5]=[CH:4][N:3]=1.[CH2:15]([NH:17][C:18](=[O:35])[NH:19][C:20]1[CH:25]=[CH:24][C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][CH:21]=1)C.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O>[CH3:15][NH:17][C:18]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]3[CH3:14])[CH:5]=[CH:4][N:3]=2)=[CH:22][CH:21]=1)=[O:35]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (S)-4-(2-chloropyrimidin-4-yl)-3-methylmorpholine (Intermediate 3) (100 mg, 0.47 mmol) and 4-(3-ethylureido)phenylboronic acid pinacol ester (143 mg, 0.52 mmol) in DME:EtOH:H2O (12:5:3, 2 mL) was added Pd(PPh3)2(Cl)2 (17 mg, 0.024 mmol) and Na2CO3 (149 mg, 1.41 mmol). The reaction mixture was then heated by microwave at 120° C. for 1 h. The crude reaction mixture was then partitioned between water and EtOAc, the phases separated and the organic layer washed with aqueous NaHCO3 and brine, dried over magnesium sulfate, filtered and the solvent removed in vacuo. The residue was purified by flash chromatography (2-5% MeOH/DCM) to yield a white solid (12 mg, 8%).

Workup

customThe crude reaction mixture
customwas then partitioned between water and EtOAc
customthe phases separated
washthe organic layer washed with aqueous NaHCO3 and brine
dry with materialdried over magnesium sulfate
filtrationfiltered
customthe solvent removed in vacuo
customThe residue was purified by flash chromatography (2-5% MeOH/DCM)

Sources & evidence

ORD record: ord-85683600bd364f7bab535de1b09c21c5
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249129B2

Reaction notes

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