HCID 59568620, compound → HCID 49783667, compound

HRID 216916Notes

Reaction equation

HRID 216916 reaction equation
[C:1]([C@@H:3]([NH:18][C:19]([C:21]1([NH:27]C(=O)OC(C)(C)C)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:27][C:21]1([C:19]([NH:18][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]([F:17])=[CH:15][CH:16]=3)=[CH:7][CH:6]=2)=[O:20])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

3

Reactant 1

HCID 59568620HCID 59568620, compound

Product 1

HCID 49783667HCID 49783667, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To (S)-tert-butyl 4-(1-cyano-2-(4′-fluorobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 4, step (ii(i)), 218 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 separated, dried and evaporated to afford the titled compound (100 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. customThe dichloromethane was separated
  10. customdried
  11. customevaporated

Sources & evidence

ORD record
ord-be76532fc58d4788bd8a5c9869c1d619
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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