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

HRID 626714Notes

Reaction equation

HRID 626714 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]([Cl:19])=[CH:4][N:3]=1.[C:20](=[O:27])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH2:21].[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].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>[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]([Cl:19])=[CH:4][N:3]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 866970524bromo-7-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671401[7-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-carbamic acid tert-butyl esterYield 121.1%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-bromo-7-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (400 mg, 1.06 mmol), tert-butyl carbamate (619 mg, 5.3 mmol), Pd2(dba)3 (48 mg, 0.05 mmol), Xantphos (61 mg, 0.1 mmol) and potassium phosphate tribasic (449 mg, 2.1 mmol) in toluene (10 mL) and water (2.0 mL) was purged with argon and heated at 70° C. for 3 hours. The reaction mixture was filtered through Celite® and washed with ethyl acetate. The filtrate was washed with water and brine, dried over sodium sulphate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (531 mg, contaminated with residual tert-butyl carbamate). LCMS (Method D): RT=3.76 min, m/z: 413 [M+H+].

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with water and brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-7e5aa8b72fd442cb9d42801777fb2e1e
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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