Cesium carbonate → [2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-(2,6-dimethylpyrimidin-4-yl)amine

HRID 626660

Reaction equation

HRID 626660 reaction equation
Cl[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[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]=[C:22]([CH3:27])[N:21]=1.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(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[Cl:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:19][C:20]3[CH:25]=[C:24]([CH3:26])[N:23]=[C:22]([CH3:27])[N:21]=3)=[N:3][CH:4]=[CH:5][C:6]2=[N:10]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 680392,6-Dimethyl-4-aminopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970364-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671258[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-(2,6-dimethylpyrimidin-4-yl)amineYield 86.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (200 mg, 0.57 mmol), 4-amino-2,6-dimethylpyrimidine (95 mg, 0.77 mmol), Pd2(dba)3 (16 mg, 0.018 mmol), Xantphos (39 mg, 0.067 mmol) and cesium carbonate (437 mg, 1.34 mmol) in dioxane (5 mL) was sealed in a microwave vial, purged with nitrogen and irradiated at 150° C. for 25 minutes in the microwave. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (60-80% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (189 mg, 73% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.52 (br s, 1H), 9.16 (s, 1H), 8.34 (s, 1H), 7.99 (d, J=6.4 Hz, 1H), 7.83 (d, J=1.0 Hz, 1H), 7.81 (s, 1H), 7.71 (dd, J=9.0, 7.3 Hz, 1H), 7.21 (d, J=6.4 Hz, 1H), 3.32 (s, 3H), 2.41 (s, 3H). LCMS (Method B): RT=2.93 min, m/z: 385 [M+H+].

Workup

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 25 minutes in the microwave
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (60-80% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-d5679c8a3f054827b0927fe2043be0bd
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Linked notes

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