(S)-tert-butyl 4-(1-cyano-2-(4'-(isopropylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate → (S)-4-Amino-N-(1-cyano-2-(4'-(isopropylsulfonyl)biphenyl-4-yl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216917Notes

Reaction equation

HRID 216917 reaction equation
[C:1]([C@@H:3]([NH:23][C:24]([C:26]1([NH:32]C(=O)OC(C)(C)C)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:25])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:32][C:26]1([C:24]([NH:23][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:16]=[CH:15][C:14]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])=[CH:13][CH:12]=3)=[CH:9][CH:10]=2)=[O:25])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1

Participants

3

Reactant 1

HCID 59568606(S)-tert-butyl 4-(1-cyano-2-(4'-(isopropylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783668(S)-4-Amino-N-(1-cyano-2-(4'-(isopropylsulfonyl)biphenyl-4-yl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 27.2%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To (S)-tert-butyl 4-(1-cyano-2-(4′-(isopropylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 4, step (ii(ii)), 300 mg) was added formic acid (4 mL) and the mixture heated to 50° C. for 20 min. The mixture was evaporated to dryness, dissolved in methanol (10 mL), re-evaporated to dryness, dissolved in methanol (6 mL) and purified on reverse phase HPLC eluting with 25 to 95% methanol in 0.1% aqueous TFA on a Waters SunFire column. The material was converted to free base by evaporating the relevant fractions, dissolving in dichloromethane (20 mL) and shaking with saturated sodium bicarbonate solution (20 mL). The dichloromethane was dried and evaporated to afford the titled compound (67 mg).

Workup

  1. customThe mixture was evaporated to dryness
  2. dissolutiondissolved in methanol (10 mL)
  3. customre-evaporated to dryness
  4. dissolutiondissolved in methanol (6 mL)
  5. custompurified on reverse phase HPLC
  6. washeluting with 25 to 95% methanol in 0.1% aqueous TFA on a Waters SunFire column
  7. customby evaporating the relevant fractions
  8. dissolutiondissolving in dichloromethane (20 mL)
  9. dry with materialThe dichloromethane was dried
  10. customevaporated

Sources & evidence

ORD record
ord-7fd3acf82b6442948e181f669092aee4
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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