Potassium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(3'-cyano-4'-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216953Notes

Reaction equation

[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1.[C:30]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:37]=1[F:38])#[N:31].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:34]2[CH:35]=[CH:36][C:37]([F:38])=[C:32]([C:30]#[N:31])[CH:33]=2)=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 75 °C

Procedure

(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iii), 346 mg) in acetonitrile (10 mL) under nitrogen was treated with 3-cyano-4-fluorophenylboronic acid (110 mg) followed by aqueous potassium carbonate solution (2M, 0.67 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (9 mg). The mixture was stirred at 75° C. for 18 h. The reaction mixture was evaporated, dissolved in dichloromethane, absorbed onto silica and purified by chromatography on silica eluting with 50% ethyl acetate in isohexane, then 100% ethyl acetate to afford the titled compound (366 mg).

Workup

customThe reaction mixture was evaporated
dissolutiondissolved in dichloromethane
customabsorbed onto silica
custompurified by chromatography on silica eluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-bed50905cfe943588fa05184691e5a9e
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193239B2

Reaction notes

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