Ethyl Acetate → HCID 9806292, compound

HRID 861149Notes

Reaction equation

HRID 861149 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:28]4[CH:29]=[C:30]([OH:34])[CH:31]=[CH:32][CH:33]=4)[C:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]5[CH2:27][CH2:26][CH2:25][CH2:24]5)[N:17]=4)=[C:11]3[CH:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:42][CH:43]1[CH2:45][CH2:44]1.C(OCC)(=O)C>C(#N)C>[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH2:42][CH:43]5[CH2:45][CH2:44]5)[CH:29]=4)[C:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]5[CH2:24][CH2:25][CH2:26][CH2:27]5)[N:17]=4)=[C:11]3[CH:10]=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 10275983HCID 10275983, compound

Product 1

HCID 9806292HCID 9806292, compoundYield 71.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-{7-(cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}phenol (400 mg, 0.88 mmol) in acetonitrile (80 mL) was added cesium carbonate (315 mg, 0.97 mmol) and (bromomethyl)-cyclopropane (0.26 mL, 2.64 mmol). The reaction mixture was heated at reflux for 6 hours. After the reaction was cooled to room temperature, ethyl acetate was added and the organic phase was washed with water, brine and dried over magnesium sulfate. Filtration and concentration followed by purification with silica gel chromatography (3:2 hexanes/ethyl acetate) gave N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine (320 mg, 71%) as yellow solid. 1H NMR (CDCl3): δ 7.97 (d, 1H), 7.78 (d, 1H), 7.33 (m, 2H), 7.18 (m, 2H), 6.98 (m, 1H), 6.30 (d, 1H), 6.02 (m, 2H), 5.08 (d, 1), 4.35 (m, 1H), 3.99 (m, 1H), 3.80 (d, 2H), 2.014 (m, 4H), 1.83–1.55 (m, 12H), 1.22 (m, 1H), 0.61 (m, 2H), 0.35 (m, 2H). MS m/z 509 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 6 hours
  3. washthe organic phase was washed with water, brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationFiltration and concentration
  6. customfollowed by purification with silica gel chromatography (3:2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-6318b835d3b24dbfa4b1e83bb7adda98
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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