Potassium Acetate → (S)-tert-Butyl 4-(2-(4'-carbamoyl-3'-fluorobiphenyl-4-yl)-1-cyanoethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216961Notes

Reaction equation

[C:1]([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)#[N:2].[C:29]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][C:33]=1[F:41])(=[O:31])[NH2:30].C([O-])(=O)C.[K+]>C(#N)C.O>[C:29]([C:32]1[CH:37]=[CH:36][C:35]([C:8]2[CH:9]=[CH:10][C:5]([CH2:4][C@H:3]([NH:12][C:13]([C:15]3([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]3)=[O:14])[C:1]#[N:2])=[CH:6][CH:7]=2)=[CH:34][C:33]=1[F:41])(=[O:31])[NH2:30]

Participants

Conditions

Temperature: 85 °C

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(4-iodophenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 15, step (i), 200 mg) and 4-carbamoyl-3-fluorophenylboronic acid (73 mg) in acetonitrile (8 mL) were treated with potassium acetate (79 mg) in water (4 mL). Nitrogen was bubbled through the mixture and then 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added and the mixture was heated at 85° C. for 18 h under nitrogen. The reaction mixture was evaporated onto silica and purified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0) to afford the sub-titled compound (108 mg).

Workup

customNitrogen was bubbled through the mixture
addition1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added
customThe reaction mixture was evaporated onto silica
custompurified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0)

Sources & evidence

ORD record: ord-bfca6372e5604ccfa058317728dd7013
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193239B2

Reaction notes

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