Dimethylformamide → HCID 45136965, compound

HRID 1361132Notes

Reaction equation

HRID 1361132 reaction equation
Br[C:2]1[CH:7]=[C:6]([C@@H:8]([NH:11][C:12]([C:14]2[C:15]3[CH:22]=[N:21][N:20]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:16]=3[CH:17]=[N:18][CH:19]=2)=[O:13])[CH2:9][CH3:10])[CH:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:49][N:50](C=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N>[C:49]([C:2]1[CH:7]=[C:6]([C@@H:8]([NH:11][C:12]([C:14]2[C:15]3[CH:22]=[N:21][N:20]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:16]=3[CH:17]=[N:18][CH:19]=2)=[O:13])[CH2:9][CH3:10])[CH:5]=[CH:4][N:3]=1)#[N:50]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 59278146HCID 59278146, compound

Product 1

HCID 45136965HCID 45136965, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
140 °C

Procedure

A microwave vial charged with 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [(S)-1-(2-bromopyridin-4-yl)-propyl]-amide (0.10 g, 0.22 mmol), PS-triphenylphosphine (20 mg, 0.04 mmol), palladium (II) acetate (5 mg, 0.02 mmol), zinc cyanide (26 mg, 0.22 mmol) and DMF (2 mL) was warmed in a microwave at 140° C. After 30 minutes, additional zinc cyanide (25 mg, 0.22 mmol) was added and the mixture was warmed in a microwave at 140° C. After 30 minutes, the mixture was filtered washing with diethyl ether. The filtrate was diluted with ether and washed with water (2×40 mL) and brine (40 mL). The organic layer was dried over sodium sulfate and concentrated. The crude material was purified by reversed-phase HPLC. The desired fractions from the column were concentrated diluted with saturated aqueous sodium bicarbonate and extracted with dichloromethane (2×25 mL), dried with sodium sulfate and concentrated to afford the title compound.

Workup

  1. temperaturethe mixture was warmed in a microwave at 140° C
  2. waitAfter 30 minutes
  3. filtrationthe mixture was filtered
  4. washwashing with diethyl ether
  5. additionThe filtrate was diluted with ether
  6. washwashed with water (2×40 mL) and brine (40 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was purified by reversed-phase HPLC
  10. concentrationThe desired fractions from the column were concentrated
  11. additiondiluted with saturated aqueous sodium bicarbonate
  12. extractionextracted with dichloromethane (2×25 mL)
  13. dry with materialdried with sodium sulfate
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-98982aa1000c4f048e63ccba9bc85da9
Source dataset
uspto-grants-2011_02
Patent number
US07879873B2

Reaction notes

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