Cesium carbonate → 2-[5-cyclopropyl-1-(4-methoxybenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1774542Notes

Reaction equation

HRID 1774542 reaction equation
[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[N:7]=[C:6]([C:18]3[N:23]=[C:22]([NH2:24])[C:21]([O:25][CH3:26])=[CH:20][N:19]=3)[C:5]=2[CH3:27])[CH2:3][CH2:2]1.Cl.Br[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[N:7]=[C:6]([C:18]3[N:23]=[C:22]([NH:24][C:30]4[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=4)[C:21]([O:25][CH3:26])=[CH:20][N:19]=3)[C:5]=2[CH3:27])[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 896482282-[5-cyclopropyl-1-(4-methoxybenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxypyrimidin-4-amine

Product 1

HCID 716118872-[5-cyclopropyl-1-(4-methoxybenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

1.03 g of 2-[5-cyclopropyl-1-(4-methoxybenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxypyrimidin-4-amine (2.82 mmol, 1.00 eq.), 603 mg of 4-bromopyridine hydrochloride (1:1) (3.10 mmol, 1.10 eq.), 245 mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.423 mmol, 0.15 eq.), 2.76 g of cesium carbonate (8.46 mmol, 3.00 eq.) and 63 mg of palladium diacetate (0.282 mmol, 0.1 eq.) were suspended in 10.8 mL of dry DMF and stirred under nitrogen atmosphere at 105° C. bath temperature for two hours. The reaction mixture was diluted with water and the crude product was extracted with DCM. The combined organic layers were dried over a silicon filter and concentrated in vacuo. The residue was purified by flash chromatography yielding 930 mg (1.95 mmol, 69%) of analytically pure target compound.

Workup

  1. extractionthe crude product was extracted with DCM
  2. customThe combined organic layers were dried over a silicon
  3. filtrationfilter
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. customyielding 930 mg (1.95 mmol, 69%) of analytically pure target compound

Sources & evidence

ORD record
ord-f925d1a0cb274cb381e5c10874b551ef
Source dataset
uspto-grants-2016_02
Patent number
US09260412B2

Reaction notes

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