Ethyl Acetate → N-[2-Methoxy-4-(6-([(1S)-1-pyridin-3-ylbutyl]amino)pyrazin-2-yl)phenyl]-N'-ethylurea

HRID 2280878Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH2:10][CH2:11][CH3:12])[CH:5]=[N:4][CH:3]=1.[C:19](=[O:22])([O-])[O-].[Na+].[Na+].[C:25]([O:28][CH2:29][CH3:30])(=O)C>C(O)CC.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][O:28][C:29]1[CH:30]=[C:12]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([NH:8][C@H:9]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[CH2:10][CH2:11][CH3:12])[N:7]=2)[CH:11]=[CH:10][C:9]=1[NH:8][C:19]([NH:4][CH2:3][CH3:2])=[O:22]

Participants

Conditions

Temperature: 100 °C

Procedure

Under a nitrogen atmosphere a mixture of 6-chloro-N-[(1S)-1-pyridin-3-ylbutyl]pyrazin-2-amine (53 g, 0.2 mmol), 4-{[(ethylamino)carbonyl]amino}-3-methoxyphenylboronic acid pinacol diester (69 mg, 0.23 mmol), tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.02 mmol) in toluene-n-propanol (2.6 mL, 3:1) was treated with 2M aqueous sodium carbonate solution (0.15 mL, 0.3 mmol). The resulting mixture was stirred vigorously whilst being heated at 100° C. for 22 hours. Once cool ethyl acetate (10 mL) was added and the mixture washed with H2O (6×10 mL) and brine (10 mL) and then dried (Na2SO4). Removal of solvent in vacuo then yielded crude product, which was purified by column chromatography using dichloromethane-methanol-aqueous ammonia (93:7:1) as eluent to furnish the product (60 mg).

Workup

washthe mixture washed with H2O (6×10 mL) and brine (10 mL)
dry with materialdried (Na2SO4)
customRemoval of solvent in vacuo
customthen yielded crude product, which
customwas purified by column chromatography

Sources & evidence

ORD record: ord-98667148ad2247ebbec238c976532684
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139560B2

Reaction notes

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