(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 216991Notes

Reaction equation

HRID 216991 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

3

Reactant 1

HCID 59568556(S)-tert-Butyl 4-(1-cyano-2-(4'-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 497836664-Amino-N-[(1S)-1-cyano-2-(4'-cyano[1,1'-biphenyl]-4-yl)ethyl]tetrahydro-2H-pyran-4-carboxamideYield 50.7%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
40 °C

Procedure

To (S)-tert-butyl 4-(1-cyano-2-(4′-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (produced in step (iii), 5 g) was added formic acid (6 rel. vol.) at room temperature and the mixture heated to 40° C. The reaction mixture was stirred for 1.5 h at 40° C. and then cooled to 0-8° C. and quenched with water (5 rel. vol.). The reaction mixture was diluted with 2-methyltetrahydrofuran (10 rel. vol.) and 2N NaOH solution added dropwise at 0-8° C. until the pH reached 6.7. The reaction mixture was further diluted with 2-2-methyltetrahydrofuran (10 rel. vol.) and extracted. The organic layer was separated and concentrated to 8 rel. vol. under vacuum. The mixture was stirred the concentrated for 1 h at room temperature and the resulting solid was filtered and washed with 2-methyltetrahydrofuram (1 rel. vol.) to afford the titled compound (2.0 g).

Workup

  1. temperaturecooled to 0-8° C.
  2. customquenched with water (5 rel. vol.)
  3. additionThe reaction mixture was diluted with 2-methyltetrahydrofuran (10 rel. vol.) and 2N NaOH solution
  4. additionadded dropwise at 0-8° C. until the pH
  5. additionThe reaction mixture was further diluted with 2-2-methyltetrahydrofuran (10 rel. vol.)
  6. extractionextracted
  7. customThe organic layer was separated
  8. concentrationconcentrated to 8 rel
  9. stirringThe mixture was stirred the
  10. concentrationconcentrated for 1 h at room temperature
  11. filtrationthe resulting solid was filtered
  12. washwashed with 2-methyltetrahydrofuram (1 rel. vol.)

Sources & evidence

ORD record
ord-7abc7f0b039144cf93345d75685b630a
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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