Potassium Carbonate → N-cyclopentyl-8-[2-(cyclopentylamino)-4-pyrimidinyl]-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine

HRID 1296723Notes

Reaction equation

[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15](I)=[C:11]3[N:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CSC1N=C([Sn](CCCC)(CCCC)CCCC)C=CN=1.[CH:44]1([NH:49][C:50]2[N:55]3N=C(C4C=CC=CC=4)[C:58]([C:59]4C=CN=C(SC)[N:60]=4)=[C:54]3N=CN=2)[CH2:48][CH2:47][CH2:46][CH2:45]1.C1(NC2N3N=C(C4C=CC=CC=4)C=C3N=CN=2)CCCC1.ClC1C=C(C=CC=1)C(OO)=O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.ClCCl.C1(N)CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(OCC)(=O)C>[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15]([C:59]4[CH:58]=[CH:54][N:55]=[C:50]([NH:49][CH:44]5[CH2:45][CH2:46][CH2:47][CH2:48]5)[N:60]=4)=[C:11]3[N:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

N-Cyclopentyl-8-iodo-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine (80 mg, 0.20 mmol) was dissolved in anhydrous toluene (5 mL). To this solution was added 2-(methylsulfanyl)-4-(tributylstannyl)pyrimidine (100 mg, 0.24 mmol,) and dichlorobis(triphenylphosphine)palladium (II] (14 mg, 0.1 equiv) and the resulting mixture heated at 100° C. for 24 hours. Ethyl acetate and water were added to the reaction mixture. The phases were separated and the organic phase washed with water, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (ethyl acetate:hexane 1:1) gave an inseparable mixture of the desired N-cyclopentyl-8-[2-(methylsulfanyl)-4-pyrimidinyl]-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine contaminated with N-cyclopentyl-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine. This mixture was dissolved in dichloromethane (15 mL) and 3-chloroperoxybenzoic acid (113 mg, 57–86%) was added. The resulting reaction mixture was stirred at room temperature for 1 hour. Dichloromethane and saturated aqueous potassium carbonate were added and the phases separated. The organic phase was washed with additional saturated aqueous potassium carbonate, water, dried over magnesium sulfate, filtered and concentrated to give a foam. This foam was dissolved in cyclopentylamine and the solution was heated at 60° C. for 3 hours. The mixture was concentrated in vacuo and the residue purified by silica gel chromatography (ethyl acetate:hexane 1:1) to give 20 mg (23% for 3 steps) of N-cyclopentyl-8-[2-(cyclopentylamino)-4-pyrimidinyl]-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine as a white foam. 1H-NMR (CDCl3): δ 8.39 (s, 1H), 8.28 (d, 1H), 7.67 (m, 2H), 7.46 (3H), 6.71 (d, 1H), 5.01 (d, 1H), 4.64 (m, 1H), 3.80 (m, 1H), 1.2–2.3 (m, 16H); MS m/z 441 (M+1).

Workup

customThe phases were separated
washthe organic phase washed with water
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by silica gel chromatography (ethyl acetate:hexane 1:1)
customgave
customThe resulting reaction mixture
customthe phases separated
washThe organic phase was washed with additional saturated aqueous potassium carbonate, water
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give a foam
temperaturethe solution was heated at 60° C. for 3 hours
concentrationThe mixture was concentrated in vacuo
customthe residue purified by silica gel chromatography (ethyl acetate:hexane 1:1)

Sources & evidence

ORD record: ord-dc075bd2d2844a81b690b0cf7eb59254
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07247626B2

Reaction notes

Loading…