Cesium carbonate → [7-Bromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

HRID 626734Notes

Reaction equation

HRID 626734 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]([Br:19])=[CH:4][N:3]=1.[CH3:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH2:27])[CH:22]=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]>[Br:19][C:5]1[C:6]2[C:7](=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=2)[C:2]([NH:27][C:23]2[CH:22]=[C:21]([CH3:20])[N:26]=[CH:25][N:24]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970594,7-Dibromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671843[7-Bromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amineYield 64%

Reagents, catalysts & solvents 2

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

Procedure

A suspension of 4,7-dibromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (317 mg, 0.75 mmol), 6-methylpyrimidin-4-ylamine (90 mg, 0.83 mmol), Pd2(dba)3 (17 mg, 0.019 mmol), Xantphos (43 mg, 0.075 mmol) and cesium carbonate (489 mg, 1.5 mmol) in dioxane (11 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated in a microwave reactor at 150° C. for 1 hour. 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 (50-60% ethyl acetate in cyclohexane), to afford the title compound as a yellow solid (215 mg, 64% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.80 (s, 1H), 9.29 (s, 1H), 8.72 (d, J=1.3 Hz, 1H), 8.40 (s, 1H), 8.17 (s, 1H), 7.85 (d, J=0.9 Hz, 1H), 7.82 (s, 1H), 7.74 (dd, J=7.1 and 9.0 Hz, 1H), 2.46 (s, 3H). LCMS (Method B): RT=3.60 min, m/z: 449 [M+H+].

Workup

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated in a microwave reactor at 150° C. for 1 hour
  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 (50-60% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-7d56eae8ea0f441e96120f3e909b38e3
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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