Cyclopentylamine → HCID 10277523, compound

HRID 861147Notes

Reaction equation

HRID 861147 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[CH:26]=3)[C:10]([C:11]3[C:16]([CH3:17])=[C:15]([CH3:18])[N:14]=[C:13]([NH:19][CH:20]4[CH2:24][CH2:23][CH2:22][CH2:21]4)[N:12]=3)=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH:32]1([NH2:37])[CH2:36][CH2:35][CH2:34][CH2:33]1>>[CH:32]1([NH:37][C:2]2[N:7]3[N:8]=[C:9]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[CH:26]=4)[C:10]([C:11]4[C:16]([CH3:17])=[C:15]([CH3:18])[N:14]=[C:13]([NH:19][CH:20]5[CH2:24][CH2:23][CH2:22][CH2:21]5)[N:12]=4)=[C:6]3[CH:5]=[CH:4][CH:3]=2)[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

3

Reactant 2

HCID 2906CyclopentylamineHCID 58765485HCID 58765485, compound

Product 1

HCID 10277523HCID 10277523, compoundYield 44%

Conditions

Temperature
90 °C

Procedure

A mixture of 4-[7-chloro-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-5,6-dimethyl-2-pyrimidinamine (80 mg, 0.19 mmol) and cyclopentylamine (2 mL, 20 mmol) was heated in a sealed tube at 90° C. for 3 hours followed by 125° C. for 24 hours. The reaction mixture was cooled to room temperature and excess cyclopentylamine was removed in vacuo. The crude residue was washed with saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate. The combined extracts were washed with water and brine then dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (5:1 hexanes:ethyl acetate) provided N-cyclopentyl-3-[2-(cyclopentylamino)-5,6-dimethyl-4-pyrimidinyl]-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-7-amine (40 mg, 44%) as a clear oil. Rf 0.32 (4:1 hexanes:ethyl acetate); 1H NMR (CDCl3) δ 7.57 (s, 1H), 7.33 (d, 1H), 7.19–7.11 (m, 3H), 6.91 (d, 1H), 6.03 (d, 1H), 6.93 (d, 1H), 4.91 (d, 1H), 4.29 (m, 1H), 4.01 (m, 1H), 2.34 (s, 3H), 2.28 (s, 3H), 2.15 (m, 2H), 1.99 (broad, 2H), 1.87–1.40 (m, 15H); MS m/z 481 (M+1). To a solution of the product (20 mg) in ether was added 1 M HCl in ether. The precipitated solid was isolated to give the corresponding HCl salt.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customexcess cyclopentylamine was removed in vacuo
  3. washThe crude residue was washed with saturated aqueous sodium bicarbonate solution
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined extracts were washed with water and brine
  6. dry with materialthen dried over magnesium sulfate
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-7564600445f74cf2918882e9019b8eca
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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