Sodium ethoxide → HCID 10202410, compound

HRID 1373821Notes

Reaction equation

HRID 1373821 reaction equation
Cl.[CH:2]1([NH:7][C:8]([NH2:10])=[NH:9])[CH2:6][CH2:5][CH2:4][CH2:3]1.[O-]CC.[Na+].[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]([CH3:28])=[CH2:27])=[C:20]2[CH:19]=[CH:18][CH:17]=1>C(O)C.[Pd].C(OCC)(=O)C>[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[C:26]([CH3:28])=[CH:27][N:10]=[C:8]([NH:7][CH:2]4[CH2:6][CH2:5][CH2:4][CH2:3]4)[N:9]=3)=[C:20]2[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 3

HCID 2723922Sodium ethoxide2×HCID 86616862HCID 86616862, compoundHCID 178479367HCID 178479367, compound2×

Product 1

HCID 10202410HCID 10202410, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-cyclopentylguanidine hydrochloride (68 mg, 0.42 mmol) in ethanol (1 mL) was added sodium ethoxide (138 μL, 3 M in ethanol, 0.41 mmol). A solution of 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-methyl-2-propen-1-one in ethanol (1 mL) was added and the reaction mixture was allowed to stir at room temperature for 16 hours. An additional aliquot of N-cyclopentylguanidine hydrochloride (68 mg, 0.42 mmol) and sodium ethoxide (138 μL, 3 M in ethanol, 0.41 mmol) in ethanol (1 ml) was added to reaction mixture and allowed to stir an additional 24 hours. Palladium on carbon (10%, 30 mg) was added to reaction mixture and allowed to stir at room temperature for 30 minutes under an atmosphere of air, at which point additional palladium on carbon (10%, 100 mg) was added. The reaction mixture was allowed to stir at room temperature 16 hours. The suspension was diluted with ethyl acetate and filtered through Celite. Concentration followed by flash chromatography (4:1 hexanes:ethyl acetate) provided 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-N-cyclopentyl-5-methyl-2-pyrimidinamine (57 mg, 43%) as a clear oil. Rf 0.24 (4:1 hexanes:ethyl acetate); 1H NMR (CDCl3) δ 8.14 (s, 1H), 7.64 (m, 2H), 7.57 (d, 1H), 7.17 (m, 1H), 7.08 (t, 2H), 7.00 (d, 1H), 5.09 (d, 1H), 4.26 (m, 1H), 2.03 (m, 2H), 1.82–1.45 (m, 9H); MS m/z 422 (M+1). To a solution of the product in ether was added 1 M hydrochloride in ether. The precipitated solid was isolated to give the corresponding hydrochloride salt.

Workup

  1. stirringto stir an additional 24 hours
  2. additionwas added
  3. stirringto stir at room temperature 16 hours
  4. filtrationfiltered through Celite
  5. concentrationConcentration

Sources & evidence

ORD record
ord-aacacc94ef114581ab33c11806d888ab
Source dataset
uspto-grants-2007_01
Patent number
US07163940B2

Reaction notes

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