Cyclopentylamine → 3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-isopropyl-2-(4-methoxyphenyl)pyrazolo[1,5-alpha]pyridin-5-amine

HRID 724008Notes

Reaction equation

HRID 724008 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:12]=3)=[C:4]2[CH:3]=1.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+].C(OCC)(=O)C.[CH:89]1([NH2:94])[CH2:93]CC[CH2:90]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:18]1([NH:17][C:13]2[N:12]=[C:11]([C:10]3[C:9]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=4)=[N:8][N:5]4[CH:6]=[CH:7][C:2]([NH:94][CH:89]([CH3:93])[CH3:90])=[CH:3][C:4]=34)[CH:16]=[CH:15][N:14]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 102238594-[5-chloro-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine

Product 1

HCID 101142893-[2-(cyclopentylamino)-4-pyrimidinyl]-N-isopropyl-2-(4-methoxyphenyl)pyrazolo[1,5-alpha]pyridin-5-amineYield 58%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

To a solution of 4-[5-chloro-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (100 mg, 0.24 mmol) in cyclopentylamine (50 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (71 mg, 0.11 mmol), cesium carbonate (155 mg, 0.48 mmol) and palladium (II) acetate (16 mg, 0.07 mmol). The resultant mixture was heated to 95° C. for 2 days at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ethyl acetate was added. The organic layer was washed with water and brine. The aqueous layer was extracted with ethyl acetate and the combined organics dried over magnesium sulfate. Filtration and concentration, followed by flash chromatography (3:2 hexanes:ethyl acetate) provided 3-[2-(cyclopentylamino)-4-pyrimidinyl]N-isopropyl-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridin-5-amine (62 mg, 58%) as a yellow solid. 1H NMR (CDCl3) δ 8.13 (d, 1H), 7.91 (d, 1H), 7.50 (d, 2H), 7.44 (d, 1H), 6.93 (d, 2H), 6.25 (d, 1H), 6.19 (dd, 1H), 5.25 (d, 1H), 4.41 (m, 1H), 4.05 (d, 1H), 3.83 (s, 3H), 3.69 (m, 1H), 2.08–2.02 (m, 2H), 1.71–1.48 (m, 6H), 1.23 (d, 6H); MS m/z 443 (M+1).

Workup

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

Sources & evidence

ORD record
ord-982e136512904c2ca9202dda87b88c59
Source dataset
uspto-grants-2006_11
Patent number
US07141569B2

Reaction notes

Loading…