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

HRID 626768Notes

Reaction equation

HRID 626768 reaction equation
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([N+:18]([O-:20])=[O:19])=[CH:13][C:12]=3[Cl:21])[N:10]=[C:6]2[C:5]([F:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26][N:25]=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:21][C:12]1[CH:13]=[C:14]([N+:18]([O-:20])=[O:19])[CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:23][C:24]3[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26][N:25]=3)=[N:3][CH:4]=[C:5]([F:22])[C:6]2=[N:10]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 866970694-Bromo-2-(2,6-dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671549[2-(2,6-Dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amineYield 81.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

A mixture of 4-bromo-2-(2,6-dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (200 mg, 0.49 mmol), 4-amino-6-methylpyrimidine (60 mg, 0.55 mmol), Pd2(dba)3 (11 mg, 0.012 mmol), Xantphos (28 mg, 0.049 mmol) and cesium carbonate (321 mg, 0.99 mmol) in dioxane (3 mL) was de-gassed and purged with nitrogen. The reaction mixture was heated at 150° C. in the microwave for 30 minutes. The resultant mixture was partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate (×4) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50-100% ethyl acetate in cyclohexane) to afford the title compound as a pale yellow solid (173 mg, 72% yield). 1H NMR (300 MHz, CDCl3): δ 8.69 (s, 1H), 8.44-8.40 (m, 3H), 8.25 (s, 1H), 7.91 (d, J=3.2 Hz, 1H), 7.80 (br s, 1H), 2.55 (s, 3H).

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. customThe resultant mixture was partitioned between ethyl acetate and water
  4. extractionThe aqueous layer was further extracted with ethyl acetate (×4)
  5. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (50-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-25fd64a60d5e4e8bb19cc2a3d62f18bf
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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