Cesium carbonate → HCID 69671629, compound

HRID 626752Notes

Reaction equation

HRID 626752 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.[CH:19]1([C:22]2[N:27]=[CH:26][N:25]=[C:24]([NH2:28])[CH:23]=2)[CH2:21][CH2:20]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]>[CH:19]1([C:22]2[N:27]=[CH:26][N:25]=[C:24]([NH:28][C:2]3[C:7]4=[CH:8][N:9]([C:11]5[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=5[Cl:18])[N:10]=[C:6]4[CH:5]=[CH:4][N:3]=3)[CH:23]=2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 450804916-Cyclopropylpyrimidin-4-amineHCID 866970364-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671629HCID 69671629, compoundYield 43.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (52 mg, 0.175 mmol), 6-cyclopropylpyrimidin-4-ylamine (26 mg, 0.193 mmol), Pd2(dba)3 (8 mg, 0.0088 mmol), Xantphos (10.1 mg, 0.0175 mmol) and cesium carbonate (114 mg, 0.35 mmol) in dioxane (1.5 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 120° C. in the microwave for 1 hour. The resultant mixture was filtered and washed with dioxane. The filtrate was concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (30 mg, 43% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.56 (d, J=0.9 Hz, 1H), 8.94 (d, J=1.0 Hz, 1H), 8.05 (d, J=7.3 Hz, 1H), 7.87-7.83 (m, 2H), 7.79-7.74 (m, 1H), 7.62 (dd, J=7.3, 0.9 Hz, 1H), 7.39 (s, 1H), 2.34-2.26 (m, 1H), 1.19-1.12 (m, 4H). LCMS (Method B): RT=3.17 min, m/z: 397 [M+H+].

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. filtrationThe resultant mixture was filtered
  4. washwashed with dioxane
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-22ab8f4b18924161aa1054980232ee96
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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