Ethyl Acetate → Lexibulin

HRID 1013077Notes

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])[C:5]([CH3:19])=[CH:4][N:3]=1.[C:20](=[O:23])([O-])[O-].[Na+].[Na+].[C:26]([O:29][CH2:30][CH3:31])(=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>[CH2:4]([NH:3][C:20]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([C:2]2[N:7]=[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])[C:5]([CH3:19])=[CH:4][N:3]=2)=[CH:31][C:30]=1[O:29][CH3:26])=[O:23])[CH3:5]

Participants

Conditions

Temperature: 100 °C

Procedure

Under a nitrogen atmosphere a mixture of 2-chloro-5-methyl-N-[(1S)-1-pyridin-3-ylbutyl]pyrimidin-4-amine (277 mg, 1.0 mmol), 4-{[(ethylamino)carbonyl]amino}-3-methoxyphenylboronic acid pinacol diester (416 mg, 1.3 mmol), tetrakis(triphenylphosphine)palladium(0) (116 mg, 0.1 mmol) in toluene n-propanol (12 mL, 3:1) was treated with 2M aqueous sodium carbonate solution (750 μL, 1.5 mmol). The resulting mixture was stirred vigorously whilst being heated at 100° C. for 17 hours. Once cool ethyl acetate (25 mL) was added and the mixture washed with H2O (6×15 mL), brine (20 mL) and 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 (110 mg, 57%).

Workup

washthe mixture washed with H2O (6×15 mL), brine (20 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-f98cc69093c94969b5eb7ce1cd918da7
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981900B2

Reaction notes

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