Formic Acid → HCID 49783987, compound

HRID 216984Notes

Reaction equation

HRID 216984 reaction equation
[C:1]([C@@H:3]([NH:22][C:23]([C:25]1([NH:31]C(=O)OC(C)(C)C)CCC[CH2:27][CH2:26]1)=[O:24])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[CH2:19][N:18]([CH3:20])[C:17](=[O:21])[C:14]3=[N:15][CH:16]=2)=[CH:7][CH:6]=1)#[N:2].[CH:39]([OH:41])=O.[C:42](#N)C>CO.O>[NH2:31][C:25]1([C:23]([NH:22][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:10]=[CH:9][C:8]([C:11]3[CH:12]=[C:13]4[CH2:19][N:18]([CH3:20])[C:17](=[O:21])[C:14]4=[N:15][CH:16]=3)=[CH:7][CH:6]=2)=[O:24])[CH2:26][CH2:27][O:41][CH2:39][CH2:42]1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 6342AcetonitrileHCID 86675095HCID 86675095, compound

Product 1

HCID 49783987HCID 49783987, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To (S)-tert-butyl 4-(1-cyano-2-(4-(6-methyl-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-3-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 32, step (iv), 0.186 g) was added formic acid (9.6 mL) and the mixture heated to 50° C. for 15 min. The mixture was allowed to cool to room temperature and diluted with methanol, and then evaporated to dryness. The residue was suspended in methanol, filtered and the filtrate was evaporated. The residue from the filtrate was purified by reversed phase HPLC (Waters X-Bridge column) eluting with methanol in aqueous 0.1% trifluoroacetic acid. The fractions containing the desired compound were combined and evaporated, and the residue combined with the solid collected during the filtration. The purified compound was dissolved in dichloromethane and washed with saturated aqueous sodium hydrogen carbonate solution. The organics were dried to over magnesium sulfate and evaporated, triturated with diethyl ether and evaporated to afford a white solid. The solid was suspended in water (2.2 mL) and acetonitrile (0.11 mL) and stirred at room temperature for 3 days. The resulting solid was collected by filtration and washed with water and then dried under vacuum at 50° C. to afford the titled compound (56 mg).

Workup

  1. temperatureto cool to room temperature
  2. customevaporated to dryness
  3. filtrationfiltered
  4. customthe filtrate was evaporated
  5. customThe residue from the filtrate was purified by reversed phase HPLC (Waters X-Bridge column)
  6. washeluting with methanol in aqueous 0.1% trifluoroacetic acid
  7. additionThe fractions containing the desired compound
  8. customevaporated
  9. filtrationcollected during the filtration
  10. dissolutionThe purified compound was dissolved in dichloromethane
  11. washwashed with saturated aqueous sodium hydrogen carbonate solution
  12. dry with materialThe organics were dried to over magnesium sulfate
  13. customevaporated
  14. customtriturated with diethyl ether
  15. customevaporated
  16. customto afford a white solid
  17. filtrationThe resulting solid was collected by filtration
  18. washwashed with water
  19. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-1576710d5b9342dab18482e5ec956115
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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