Cesium carbonate → HCID 69671470, compound

HRID 626783Notes

Reaction equation

HRID 626783 reaction equation
[Cl:1][C:2]1[C:3]([N:11]2[CH:21]=[C:14]3[C:15](Cl)=[N:16][CH:17]=[C:18]([F:19])[C:13]3=[N:12]2)=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[C:5]#[N:6].[CH3:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]([NH2:29])[CH:24]=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:1][C:2]1[C:3]([N:11]2[CH:21]=[C:14]3[C:15]([NH:29][C:25]4[CH:24]=[C:23]([CH3:22])[N:28]=[CH:27][N:26]=4)=[N:16][CH:17]=[C:18]([F:19])[C:13]3=[N:12]2)=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[C:5]#[N:6]

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 86697075HCID 86697075, compound

Product 1

HCID 69671470HCID 69671470, compoundYield 36%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

A mixture of 3-chloro-2-(4-chloro-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-5-fluorobenzonitrile (80 mg, 0.28 mmol), 6-methylpyrimidin-4-ylamine (30 mg, 0.27 mmol), Pd2(dba)3 (11 mg, 0.012 mmol), Xantphos (14 mg, 0.028 mmol) and cesium carbonate (160 mg, 0.49 mmol) in dioxane (1.8 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 diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane) to afford the title compound (35 mg, 36% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.84 (s, 1H), 9.44 (d, J=2.6 Hz, 1H), 8.69 (d, J=1.2 Hz, 1H), 8.37-8.30 (m, 3H), 8.01 (d, J=3.5 Hz, 1H), 2.44 (s, 3H). LCMS (Method B): RT=3.20 min, m/z: 398 [M+H+].

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. additionThe resultant mixture was diluted with ethyl acetate
  4. washwashed with water
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-f56729760abe4ff8883a03487a4f55fd
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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