(S)-tert-Butyl 4-(1-cyano-2-(4'-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate → 4-Amino-N-[(1S)-1-cyano-2-(4'-cyano[1,1'-biphenyl]-4-yl)ethyl]tetrahydro-2H-pyran-4-carboxamide

HRID 216992Notes

Reaction equation

[C:1]([C@@H:3]([NH:19][C:20]([C:22]1([NH:28]C(=O)OC(C)(C)C)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:21])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:28][C:22]1([C:20]([NH:19][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:10]=[CH:9][C:8]([C:11]3[CH:12]=[CH:13][C:14]([C:17]#[N:18])=[CH:15][CH:16]=3)=[CH:7][CH:6]=2)=[O:21])[CH2:23][CH2:24][O:25][CH2:26][CH2:27]1

Participants

Conditions

Temperature: 50 °C

Procedure

To (S)-tert-butyl 4-(1-cyano-2-(4′-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 3, step (v), 420 mg) was added formic acid (2 mL) and the mixture heated to 50° C. for 10 min. The mixture was evaporated to dryness, dissolved in methanol (4 mL) and purified on reverse phase HPLC (Water's sunfire column) eluting with a gradient of acetonitrile in 0.1% aqueous trifluoroacetic acid. Fractions containing product were evaporated to remove acetonitrile, neutralised with saturated sodium bicarbonate and extracted with dichloromethane which was dried over magnesium sulfate and evaporated to afford the titled compound (110 mg).

Workup

customThe mixture was evaporated to dryness
dissolutiondissolved in methanol (4 mL)
custompurified on reverse phase HPLC (Water's sunfire column)
washeluting with a gradient of acetonitrile in 0.1% aqueous trifluoroacetic acid
additionFractions containing product
customwere evaporated
customto remove acetonitrile
extractionextracted with dichloromethane which
dry with materialwas dried over magnesium sulfate
customevaporated

Sources & evidence

ORD record: ord-d0fe91e6bc5d46d1857c2b9e3a9db4a6
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193239B2

Reaction notes

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