Dichloromethane → 7-Methyl-2-(6-trifluoromethyl-pyridin-3-yl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one

HRID 1022439Notes

Reaction equation

HRID 1022439 reaction equation
Cl[C:2]1[NH:3][C:4](=[O:12])[C:5]2[CH:10]=[CH:9][N:8]([CH3:11])[C:6]=2[N:7]=1.[F:13][C:14]([F:25])([F:24])[C:15]1[N:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[CH3:11][N:8]1[C:6]2[N:7]=[C:2]([C:18]3[CH:19]=[N:20][C:15]([C:14]([F:25])([F:24])[F:13])=[CH:16][CH:17]=3)[NH:3][C:4](=[O:12])[C:5]=2[CH:10]=[CH:9]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 135741792HCID 135741792, compound2×

Product 1

HCID 1362471807-Methyl-2-(6-trifluoromethyl-pyridin-3-yl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-oneYield 6.81%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

A high pressure microwave reaction vial was charged with 2-chloro-7-methyl-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one (Intermediate A) (55 mg, 0.3 mmol), 6-(trifluoromethyl)pyridin-3-ylboronic acid (68.6 mg, 0.36 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (21.9 mg, 0.03 mmol), a 2M aqueous sodium carbonate solution (0.45 mL, 0.9 mmol), and ethanol (2 mL). The vessel was sealed, degassed and flushed with nitrogen three times. The reaction was then heated at 150° C. for 10 min in a Biotage microwave reactor. At this time, the resulting black mixture was concentrated in vacuo. The residue was treated with ethyl acetate (20 mL), stirred and filtered. The filtrate was concentrated in vacuo. Reverse phase chromatography (10-100% acetonitrile/water) and lyophilization afforded 7-methyl-2-(6-trifluoromethyl-pyridin-3-yl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one (6 mg, 6.81%) as a white solid. LC-MS calcd. for C13H10F3N4O [(M+H)+] 295, obsd. 294.8.

Workup

  1. customA high pressure microwave reaction
  2. customThe vessel was sealed
  3. customdegassed
  4. customflushed with nitrogen three times
  5. concentrationAt this time, the resulting black mixture was concentrated in vacuo
  6. additionThe residue was treated with ethyl acetate (20 mL)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-cf6bd087991b40ae91bdb76a83fd4064
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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