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

HRID 1062854Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1062854
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

Komponenten

8

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

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, 1H), 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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-69d2db000c1e4b98a6ccf2102da67192
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06962914B2

Notizen zur Reaktion

Wird geladen…