p-Toluenesulfonic acid monohydrate → HCID 21948669, compound

HRID 2214948Notes

Reaction equation

HRID 2214948 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:12]=3)=[C:6]2[CH:5]=[CH:4][C:3]=1[C:30](OCC)([O:34]CC)[O:31][CH2:32][CH3:33].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O.O>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:12]=3)=[C:6]2[CH:5]=[CH:4][C:3]=1[C:30]([O:31][CH2:32][CH3:33])=[O:34]

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 21948668HCID 21948668, compound

Product 1

HCID 21948669HCID 21948669, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of 4-[7-chloro-2-(4-fluorophenyl)-6-(triethoxymethyl)pyrazolo[1,5-α]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (375 mg, 0.677 mmol) in acetone (8 mL) and water (2 mL) was added p-toluenesulfonic acid monohydrate (321 mg, 1.69 mmol). The reaction mixture was stirred at room temperature for 2 hours, then quenched with ice water. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution, then concentrated in vacuo to remove the majority of the acetone. The resultant mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration, followed by flash chromatography (29:1 dichloromethane:methanol) provided ethyl 7-chloro-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine-6-carboxylate (175 mg, 54%) as a brown solid. Rf 0.08 (29:1 dichloromethane:methanol); 1H NMR (400 MHz, CDCl3) δ 8.36 (d, 1H), 8.09 (d, 1H), 7.82 (d, 1H), 7.65 (m, 2H), 7.14 (t, 2H), 6.30 (d, 1H), 5.19 (d, 1H), 4.46 (q, 2H), 4.32 (m, 1H), 2.06 (m, 2H), 1.77–1.21 (m, 9H); MS m/z 480 (M+1).

Workup

  1. customquenched with ice water
  2. concentrationconcentrated in vacuo
  3. customto remove the majority of the acetone
  4. extractionThe resultant mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-871bc1b61144441e96d751dd5f6b07e5
Source dataset
uspto-grants-2006_09
Patent number
US07109209B2

Reaction notes

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