Cesium carbonate → {6-[2-(2,6-Dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol

HRID 626740Notes

Reaction equation

HRID 626740 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]([O:19][CH3:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]([CH2:28][OH:29])[CH:23]=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:21][C:22]3[N:27]=[CH:26][N:25]=[C:24]([CH2:28][OH:29])[CH:23]=3)=[N:3][CH:4]=[C:5]([O:19][CH3:20])[C:6]2=[N:10]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21934615(6-Aminopyrimidin-4-yl)methanolHCID 866970604-Bromo-2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671394{6-[2-(2,6-Dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanolYield 41.3%

Reagents, catalysts & solvents 2

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

Procedure

A suspension of 4-bromo-2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine (135 mg, 0.36 mmol), (6-aminopyrimidin-4-yl)methanol (50 mg, 0.4 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (43 mg, 0.036 mmol) and cesium carbonate (235 mg, 0.72 mmol) in dioxane (3 mL) was sealed in a microwave vial, purged with nitrogen and irradiated at 150° C. for 1 hour 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 (0-2% methanol in ethyl acetate) to afford the title compound as a yellow solid (62 mg, 41% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.42 (s, 1H), 9.11 (s, 1H), 8.64 (d, J=0.9 Hz, 1H), 8.58 (d, J=1.2 Hz, 1H), 7.83 (d, J=1.3 Hz, 1H), 7.80 (s, 1H), 7.72 (dd, J=7.5, 9.2 Hz, 1H), 7.58 (s, 1H), 5.54 (t, J=6.0 Hz, 1H), 4.50 (d, J=6.0 Hz, 2H), 3.97 (s, 3H). LCMS (Method B): RT=2.75 min, m/z: 417 [M+H+].

Workup

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 1 hour 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 (0-2% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-922c49d06ae54776b72c48edff277dd8
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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