Tetrahydrofuran → HCID 66743407, compound

HRID 1259344Notes

Reaction equation

HRID 1259344 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][C:11]([O:16][CH3:17])=[C:12]([O:14][CH3:15])[CH:13]=2)[N:5]=[C:4]2[CH2:18][N:19]([C:22]3[CH:23]=[N:24][N:25]([CH2:27][C:28]([F:31])([F:30])[F:29])[CH:26]=3)[C:20](=[O:21])[C:3]=12.C(=O)([O-])[O-].[Na+].[Na+].[CH2:38](OB(OCC)OCC)[CH3:39].C1COCC1>C1(C)C=CC=CC=1>[CH3:15][O:14][C:12]1[CH:13]=[C:8]([C:6]2[N:5]=[C:4]3[CH2:18][N:19]([C:22]4[CH:23]=[N:24][N:25]([CH2:27][C:28]([F:31])([F:30])[F:29])[CH:26]=4)[C:20](=[O:21])[C:3]3=[C:2]([CH2:38][CH3:39])[CH:7]=2)[CH:9]=[N:10][C:11]=1[O:16][CH3:17]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 9009Triethyl borateHCID 10340Sodium CarbonateHCID 53327522HCID 53327522, compound

Product 1

HCID 66743407HCID 66743407, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

As shown in step 10-iii Scheme 10, 4-Chloro-2-(5,6-dimethoxypyridin-3-yl)-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (Compound 82, 75 mg, 0.165 mmol and a degassed solution of 2M aqueous sodium carbonate (826 uL, 1.65 mmol] were suspended in 10 mL of toluene. The reaction mixture was purged with nitrogen for 5 minutes and tetrakistriphenylphosphine palladium(0) (38 mg, 0.033 mmol] was added, followed by the addition of 2 M triethylborate solution in THF (992 μL, 1.0 mmol). The reaction vessel was sealed and heated for 14 hours at 80° C. The reaction mixture was cooled and the volatiles removed under reduced pressure. The residue was dissolved in EtOAc/DCM 1:1 and filtered. The filtrate was concentrated under reduced pressure. The product was purified by preparative thin layer chromatography produced 2-(5,6-dimethoxypyridin-3-yl)-4-ethyl-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (Compound 182, 1.1 mg): ESMS (M+1) 448.

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 minutes
  2. additiontetrakistriphenylphosphine palladium(0) (38 mg, 0.033 mmol] was added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction mixture was cooled
  5. customthe volatiles removed under reduced pressure
  6. dissolutionThe residue was dissolved in EtOAc/DCM 1:1
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe product was purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-85e68c3ba6544512a2e0220efd49ae4e
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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