Cyclopentylamine → 1-[7-(Cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone

HRID 1373786

Reaction equation

HRID 1373786 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:10]([C:11](=[O:13])[CH3:12])=[C:6]2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:27]1([NH2:32])[CH2:31][CH2:30][CH2:29][CH2:28]1.CCOCC>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH:27]1([NH:32][C:2]2[N:7]3[N:8]=[C:9]([C:14]4[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=4)[C:10]([C:11](=[O:13])[CH3:12])=[C:6]3[CH:5]=[CH:4][CH:3]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

8

Reactant 4

HCID 2906CyclopentylamineHCID 3283Diethyl EtherHCID 10796Cesium carbonateHCID 223500461-(7-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl)ethanone

Product 1

HCID 121025001-[7-(Cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanoneYield 96.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Procedure

To a solution of 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]ethanone (2.7 g, 9.5 mmol) in toluene (50 mL) was added successively racemic-BINAP (378 mg, 0.6 mmol), cesium carbonate (4.7 g, 14.3 mmol), cyclopentylamine (4.7 mL, 47.5 mmol), and palladium (II) acetate (86 mg, 0.4 mmol). The resultant mixture was heated to 95° C. for 2.5 hours at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ether was added. The organic layer was washed with water and brine. The aqueous layer was extracted with ether and the combined organics dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (4:1 hexanes-ethyl acetate) provided 1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]ethanone (3.1 g, 95%) as a yellow solid. 1H NMR (CDCl3): δ 7.62 (d, 1H), 7.55 (dd, 2H), 7.40 (t, 1H), 7.15 (t, 2H), 6.10 (d, 1H), 5.99 (d, 1H), 3.94 (m, 1H), 2.09 (s, 3H), 2.12–2.04 (m, 2H), 1.78–1.58 (m, 6H); 13C NMR (CDCl3) δ 192.63, 163.28 (d, JCF=247.3 Hz), 154.89, 142.65, 142.38, 131.66 (d, JCF=8.3 Hz) 131.09, 130.03 (d, JCF=3.8 Hz), 115.33 (d, JCF=22.0 Hz), 111.32, 105.41, 91.97, 53.81, 33.21, 30.10, 23.96; 19F NMR (CDCl3) δ −112.70; MS m/z 338 (M+1).

Workup

  1. washThe organic layer was washed with water and brine
  2. extractionThe aqueous layer was extracted with ether
  3. dry with materialthe combined organics dried over magnesium sulfate
  4. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-41dc35b953734144ae0083cef57912bb
Source dataset
uspto-grants-2007_01
Patent number
US07163940B2

Linked notes

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