Sodium Bicarbonate → 2-(4-Fluorophenyl)-3-[2-(3-hydroxypropylamino)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine

HRID 1374722Notes

Reaction equation

HRID 1374722 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][CH2:28][CH2:29][CH2:30][O:31]CC4C=CC(OC)=CC=4)[N:22]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+]>Cl.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][CH2:28][CH2:29][CH2:30][OH:31])[N:22]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:17])[F:18])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 210769724-[2-(4-fluorophenyl)-6-trifluoromethylpyrazolo[1,5-a]pyridin-3-yl]-N-(3-(4-methoxybenzyloxy)propyl)-2-pyrimidinamine

Product 1

HCID 102030182-(4-Fluorophenyl)-3-[2-(3-hydroxypropylamino)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridineYield 80%

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

A solution of 4-[2-(4-fluorophenyl)-6-trifluoromethylpyrazolo[1,5-a]pyridin-3-yl]-N-(3-(4-methoxybenzyloxy)propyl)-2-pyrimidinamine (2.1 g, 3.8 mmol) in 4N HCl/dioxane (5 mL) was stirred at room temperature for 4.5 h, then heated to reflux for 1 h. The mixture was cooled to room temperature, neutralized with saturated aqueous NaHCO3, and extracted with EtOAc. The EtOAc extracts were dried (MgSO4), filtered, and the solvent was evaporated. The residue was triturated with 2% EtOAc/hexanes to afford a solid which was collected by filtration and dried to give the title compound as a white solid, 1.31 g (80% yield). 1H NMR (acetone-d6) δ 9.20 (s, 1H), 8.73 (d, 1H, J=9.3 Hz), 8.15 (d, 1H, J=5.1 Hz), 7.77 (m, 2H), 7.64 (d, 1H, J=9.9 Hz), 7.34 (m, 2H), 6.50 (s, 1H), 6.40 (d, 1H, J=5.1 Hz), 3.60–3.70 (m, 4H), 1.88 (m, 2H). MS (+ve ion electrospray) 432 (95), (MH+).

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 h
  3. extractionextracted with EtOAc
  4. dry with materialThe EtOAc extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was triturated with 2% EtOAc/hexanes
  8. customto afford a solid which
  9. filtrationwas collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-dc9004b9cb224bd9a5ac98474036662b
Source dataset
uspto-grants-2007_01
Patent number
US07166597B2

Reaction notes

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