Potassium Phosphate, Tribasic → [2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-carbamic acid tert-butyl ester

HRID 626747Notes

Reaction equation

HRID 626747 reaction equation
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([F:19])=[CH:4][N:3]=1.[C:20](=[O:27])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH2:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([O:22][C:20](=[O:27])[NH:21][C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([F:19])=[CH:4][N:3]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970564-Bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69674902[2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-carbamic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 4-bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (635 mg, 1.75 mmol), tert-butyl carbamate (614 mg, 5.25 mmol), Pd2(dba)3 (40 mg, 0.044 mmol), Xantphos (101 mg, 0.175 mmol) and potassium phosphate tribasic (742 mg, 3.5 mmol) in toluene (15 mL) and water (3 mL) was de-gassed and purged with argon and the reaction mixture was heated at 70° C. for 5 h. The mixture was cooled and partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane) to afford the title compound as a pale yellow solid (396 mg, 57% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.19 (s, 1H), 9.05 (s, 1H), 7.92 (d, J=3.1 Hz, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.72 (d, J=7.9 Hz, 1H), 1.48 (s, 9H).

Workup

  1. customwas de-gassed
  2. custompurged with argon
  3. temperatureThe mixture was cooled
  4. custompartitioned between ethyl acetate and water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-6a3d03b7b2cb4987849e6ea9de6c5d21
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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