(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
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]1Participants
3
Reactant 1
Product 1
Reagents, catalysts & solvents 1
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 eluting with 25 to 85% acetonitrile in 0.1% TFA on a Water's Sunfire column. Fractions containing product were evaporated to remove acetonitrile, neutralised with saturated sodium bicarbonate and extracted with dichloromethane which was dried and evaporated to afford the titled compound as a solid (110 mg).
Workup
- customThe mixture was evaporated to dryness
- dissolutiondissolved in methanol (4 mL)
- custompurified on reverse phase HPLC
- washeluting with 25 to 85% acetonitrile in 0.1% TFA on a Water's Sunfire column
- additionFractions containing product
- customwere evaporated
- customto remove acetonitrile
- extractionextracted with dichloromethane which
- customwas dried
- customevaporated
Sources & evidence
- ORD record
- ord-68199a4a20674855ba1a7818c0d88a2c
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08193239B2
Reaction notes
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