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

HRID 626696Notes

Reaction equation

HRID 626696 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:20])[C:9]=1[N:10]1[CH:19]=[C:13]2[C:14](Cl)=[N:15][CH:16]=[CH:17][C:12]2=[N:11]1)[C:5]#[N:6].[C:21](=[O:28])([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH2:22].[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:24]([O:23][C:21](=[O:28])[NH:22][C:14]1[C:13]2=[CH:19][N:10]([C:9]3[C:2]([Cl:1])=[CH:3][C:4]([C:5]#[N:6])=[CH:7][C:8]=3[Cl:20])[N:11]=[C:12]2[CH:17]=[CH:16][N:15]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 866970463,5-Dichloro-4-(4-chloropyrazolo[4,3-c]pyridin-2-yl)benzonitrile

Product 1

HCID 69674840[2-(2,6-Dichloro-4-cyanophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]carbamic acid tert-butyl esterYield 123.7%

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
90 °C

Procedure

A mixture of 3,5-dichloro-4-(4-chloro-pyrazolo[4,3-c]pyridin-2-yl)-benzonitrile (3.23 g, 10 mmol), tert-butyl carbamate (5.85 mg, 50 mmol), Pd2(dba)3 (458 mg, 0.5 mmol), Xantphos (576 mg, 1.0 mmol) and potassium phosphate tribasic (4.24 g, 20 mmol) in toluene (100 mL) and water (20 mL) was degassed with argon then heated at 90° C. for 30 minutes. The reaction was cooled to room temperature and then filtered through Celite® using ethyl acetate to wash the filter pad. The filtrate was washed with water and sodium bicarbonate (sat. aq.), dried over sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane) to afford the title compound as an off-white solid (5.0 g, contaminated with residual tert-butyl carbamate). LCMS (Method D): RT=2.44 min, m/z: 348 [M−C4H7+].

Workup

  1. customwas degassed with argon
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through Celite®
  4. washto wash the filter pad
  5. washThe filtrate was washed with water and sodium bicarbonate (sat. aq.)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resultant residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-5ad18958b62b4ec4b687a774e62bd8da
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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