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

HRID 216907Notes

Reaction equation

HRID 216907 reaction equation
[C:1]([C@@H:3]([NH:22][C:23]([C:25]1([NH:31]C(=O)OC(C)(C)C)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[O:24])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH2:20][CH3:21])(=[O:19])=[O:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:31][C:25]1([C:23]([NH:22][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]([CH2:20][CH3:21])(=[O:19])=[O:18])=[CH:13][CH:12]=3)=[CH:9][CH:10]=2)=[O:24])[CH2:26][CH2:27][O:28][CH2:29][CH2:30]1

Participants

3

Reactant 1

HCID 59568561(S)-tert-butyl 4-(1-cyano-2-(4'-(ethylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783665(S)-4-Amino-N-(1-cyano-2-(4'-(ethylsulfonyl)biphenyl-4-yl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 52.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To (S)-tert-butyl 4-(1-cyano-2-(4′-(ethylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (v(ii)), 920 mg) was added formic acid (3 mL) and the mixture heated to 50° C. for 30 min. The mixture was evaporated to dryness, dissolved in methanol (9 mL) and purified on reverse phase HPLC eluting with 25 to 95% methanol in 0.1% 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 as a solid (397 mg).

Workup

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

Sources & evidence

ORD record
ord-ec13180bea404d1b84a075428da64433
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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