Cyclopentylamine → N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolid inyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-alpha]pyridin-7-amine

HRID 1796533Notes

Reaction equation

HRID 1796533 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([N:17]4[CH2:21][CH2:20][CH2:19][CH2:18]4)[N:12]=3)=[C:6]2[CH:5]=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:85]1([NH2:90])[CH2:89][CH2:88][CH2:87][CH2:86]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOCC>[CH:85]1([NH:90][C:2]2[N:7]3[N:8]=[C:9]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[C:10]([C:11]4[CH:16]=[CH:15][N:14]=[C:13]([N:17]5[CH2:21][CH2:20][CH2:19][CH2:18]5)[N:12]=4)=[C:6]3[CH:5]=[CH:4][C:3]=2[C:29]([F:32])([F:31])[F:30])[CH2:89][CH2:88][CH2:87][CH2:86]1

Participants

8

Reactant 4

HCID 2906CyclopentylamineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 221809127-Chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine

Product 1

HCID 10142258N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolid inyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-alpha]pyridin-7-amineYield 63%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 7-chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (54 mg, 0.12 mmol) in toluene (3 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (9.2 mg, 0.013 mmol), cesium carbonate (57 mg, 0.17 mmol), cyclopentylamine (0.5 mL, 5.0 mmol), and palladium (II) acetate (2 mg, 0.009 mmol). The resultant mixture was heated at 85° C. for 6 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 (12:1 to 8:1 hexanes-ethyl acetate) provided N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-amine (37 mg, 63%) as an oil. 1H NMR (CDCl3): δ 8.16 (d, 1 H), 7.84 (d, 1 H), 7.68 (dd, 2 H), 7.49 (d, 1 H), 7.18 (t, 2 H), 6.55 (d, 1 H), 6.29 (d, 1 H), 4.57 (m, 1 H), 3.68 (m, 4 H), 2.13–2.05 (m, 6 H), 1.84–1.65 (m, 6 H); 19F NMR (CDCl3) δ −55.33, −112.78; MS m/z 511 (M+1). This material was taken up in ether and treated with hydrochloric acid in ether to yield a bright yellow powder which was isolated by filtration as a hydrochloride salt.

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-6c7405c6f6ec4c898302653cdb2c78e0
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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