Ethanol → 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-6-methyl-2-pyrimidinamine

HRID 1373794Notes

Reaction equation

HRID 1373794 reaction equation
[Na].C(O)C.Cl.[CH:6]1([NH:11][C:12]([NH2:14])=[NH:13])[CH2:10][CH2:9][CH2:8][CH2:7]1.[Cl:15][C:16]1[N:21]2[N:22]=[C:23]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:24]([C:25](=O)[C:26]#[C:27][CH3:28])=[C:20]2[CH:19]=[CH:18][CH:17]=1>O>[Cl:15][C:16]1[N:21]2[N:22]=[C:23]([C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)[C:24]([C:25]3[CH:26]=[C:27]([CH3:28])[N:14]=[C:12]([NH:11][CH:6]4[CH2:10][CH2:9][CH2:8][CH2:7]4)[N:13]=3)=[C:20]2[CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 5360545Sodium2×HCID 112784021-[7-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-butyn-1-oneHCID 178479367HCID 178479367, compound

Product 1

HCID 102957644-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-6-methyl-2-pyrimidinamineYield 98%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a dry round bottom flask was added sodium metal (81 mg, 3.5 mmol). Ethanol (20 mL) was added and allowed to react with sodium at room temperature until completely dissolved. N-Cyclopentylguanidine hydrochloride (572 mg, 3.5 mmol) was added and the mixture was allowed to stir at room temperature for 10 minutes. To the resultant mixture was added 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-butyn-1-one (842 mg, 2.69 mmol) and the reaction mixture was allowed to stir at room temperature for 72 hours, then heated to 70° C. for 12 hours. The reaction mixture was cooled to room temperature and diluted with water. The mixture was extracted with ethyl acetate, and the combined extracts were washed with water and brine. The organic layer was dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (4:1 hexanes:ether to 3:2 hexanes:ether) provided 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-N-cyclopentyl-6-methyl-2-pyrimidinamine (1.11 g, 98%) as a yellow foam. Rf 0.45 (3:1 hexanes:ethyl acetate). 1H NMR (CDCl3) δ 8.35 (d, 1H), 7.64 (m, 2H), 7.24 (m, 1H), 7.13 (m, 2H), 7.03 (d, 1H), 6.22 (s, 1H), 5.10 (m, 1H), 4.35 (m, 1H), 2.19 (s, 3H), 2.03 (m, 2H), 1.60 (m, 6H); MS m/z 422 (M+1).

Workup

  1. dissolutionuntil completely dissolved
  2. stirringto stir at room temperature for 72 hours
  3. temperatureheated to 70° C. for 12 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionThe mixture was extracted with ethyl acetate
  6. washthe combined extracts were washed with water and brine
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-4790761af55d4ffe9dd77b2e89e26edb
Source dataset
uspto-grants-2007_01
Patent number
US07163940B2

Reaction notes

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