Formic Acid → (3R)-3-{[5-(4-Ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]oxy}piperidinium formate

HRID 2189074Notes

Reaction equation

HRID 2189074 reaction equation
C([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][C:15]2[C:16]3[C:23]([C:24]4[CH:29]=[CH:28][C:27]([CH2:30][CH3:31])=[CH:26][CH:25]=4)=[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[F:38])[O:21][C:17]=3[N:18]=[CH:19][N:20]=2)[CH2:9]1)C1C=CC=CC=1.[CH:39]([OH:41])=[O:40]>[Pd].CO.C(O)C>[CH:39]([O-:41])=[O:40].[CH2:30]([C:27]1[CH:28]=[CH:29][C:24]([C:23]2[C:16]3[C:15]([O:14][C@@H:10]4[CH2:11][CH2:12][CH2:13][NH2+:8][CH2:9]4)=[N:20][CH:19]=[N:18][C:17]=3[O:21][C:22]=2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[F:38])=[CH:25][CH:26]=1)[CH3:31]

Participants

5

Reactant 2

HCID 284Formic AcidHCID 582801764-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-5-(4-ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidine

Product 1

HCID 67160574(3R)-3-{[5-(4-Ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]oxy}piperidinium formate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 18681192Ethanol, mixt. with methanolSolvent

Procedure

Add 30 mg of 10% palladium on activated carbon to an argon-blanketed solution of 275 mg (0.54 mmol) of 4-{[(3R)-1-benzylpiperidin-3-yl]oxy}-5-(4-ethylphenyl)-6-(2-fluorophenyl)furo-[2,3-d]pyrimidine in 5 ml of methanol/ethanol (1:2), and stir at room temperature under a hydrogen atmosphere (standard pressure) for three hours. After adding a further 70 mg of 10% palladium on activated carbon, stir the reaction mixture for another 19 hours under a hydrogen atmosphere (standard pressure) at room temperature. Add a further 175 mg of 10% palladium on activated carbon and 0.2 ml of formic acid, and stir the reaction mixture once again at room temperature under a hydrogen atmosphere (standard pressure) for 15 hours. After filtering off the catalyst, wash the catalyst residue with methanol/water. Concentrate the filtrate under reduced pressure, take up the residue in acetonitrile/DMSO and purify by means of preparative RP-HPLC (gradient: water/acetonitrile/formic acid). 137 mg (54% of theory) of the desired product are obtained.

Workup

  1. stirringstir the reaction mixture for another 19 hours under a hydrogen atmosphere (standard pressure) at room temperature
  2. stirringstir the reaction mixture once again at room temperature under a hydrogen atmosphere (standard pressure) for 15 hours
  3. filtrationAfter filtering off the catalyst
  4. washwash the catalyst residue with methanol/water
  5. concentrationConcentrate the filtrate under reduced pressure
  6. custompurify by means of preparative RP-HPLC (gradient: water/acetonitrile/formic acid)

Sources & evidence

ORD record
ord-883fddfffd664ad2be311e4850e6d893
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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