HCID 59568577, compound → HCID 49783902, compound

HRID 216955Notes

Reaction equation

HRID 216955 reaction equation
[C:1]([C@@H:3]([NH:20][C:21]([C:23]1([NH:29]C(=O)OC(C)(C)C)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]#[N:19])[CH:12]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:29][C:23]1([C:21]([NH:20][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]([F:17])=[C:13]([C:18]#[N:19])[CH:12]=3)=[CH:9][CH:10]=2)=[O:22])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

Participants

3

Reactant 1

HCID 59568577HCID 59568577, compound

Product 1

HCID 49783902HCID 49783902, compoundYield 74.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(3′-cyano-4′-fluorobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 22, step (ii), 353 mg) was dissolved in formic acid (2.5 mL) and the reaction mixture stirred at room temperature for 3 h. The reaction mixture was evaporated to dryness, dissolved in methanol (10 mL), re-evaporated to dryness, dissolved in methanol (5.5 mL) and purified on reversed phase HPLC eluting with methanol in 0.1% aqueous TFA on a Water's SunFire column. The material was converted to free base by evaporating the relevant fractions, dissolving the residue in ethyl acetate (20 mL) and washing with saturated sodium bicarbonate solution (20 mL). The sodium bicarbonate solution was re-extracted with ethyl acetate (20 mL). The combined organic extracts were dried and evaporated to afford the titled compound (209 mg).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutiondissolved in methanol (10 mL)
  3. customre-evaporated to dryness
  4. dissolutiondissolved in methanol (5.5 mL)
  5. custompurified on reversed phase HPLC
  6. washeluting with methanol in 0.1% aqueous TFA on a Water's SunFire column
  7. customby evaporating the relevant fractions
  8. dissolutiondissolving the residue in ethyl acetate (20 mL)
  9. washwashing with saturated sodium bicarbonate solution (20 mL)
  10. extractionThe sodium bicarbonate solution was re-extracted with ethyl acetate (20 mL)
  11. customThe combined organic extracts were dried
  12. customevaporated

Sources & evidence

ORD record
ord-0accce744be645ae953a5264be7b931f
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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