Carbamate → HCID 178507612, compound

HRID 2280112Notes

Reaction equation

HRID 2280112 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][N:9]=2)[C:5]([C:17]([F:20])([F:19])[F:18])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:27](=O)([O-])[NH2:28].C[N:32]([CH:34]=O)C>C(Cl)Cl.C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:32][CH:34]1[CH2:6][CH2:5][CH:4]([CH2:27][NH:28][C:2]2[CH:3]=[CH:4][C:5]([C:17]([F:20])([F:19])[F:18])=[C:6]([C:8]3[C:16]4[C:11](=[N:12][CH:13]=[CH:14][CH:15]=4)[NH:10][N:9]=3)[N:7]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 276CarbamateHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 1785061723-(6-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 178507612HCID 178507612, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 3-(6-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine (100 mg, 0.33 mmol), K2CO3 (55.53 mg, 0.40 mmol) and tert-butyl N-[4-aminomethyl)cyclohexyl]carbamate (86.11 mg, 0.40 mmol) in DMF (1 mL) were heated at 115° C. for 8 hours. The reaction was worked up by diluting with DCM, washing with saturated aqueous bicarbonate and brine. After drying over MgSO4, the mixture was filtered and evaporated to dryness to give an orange residue. The residue was taken up in TFA/DCM (1 ml/3 ml) and stirred at RT for 2 hours. Reaction mixture was concentrated and the resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100 A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (29 mg, 17% Yield).

Workup

  1. washwashing with saturated aqueous bicarbonate and brine
  2. dry with materialAfter drying over MgSO4
  3. filtrationthe mixture was filtered
  4. customevaporated to dryness
  5. customto give an orange residue
  6. customReaction mixture
  7. concentrationwas concentrated
  8. customthe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100 A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-d2ba9f9397754f93911a840620a8eec8
Source dataset
uspto-grants-2015_09
Patent number
US09137973B2

Reaction notes

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