Diethyl Ether → 3-(2-anilinopyrimidin-4-yl)-N-cyclopentyl-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine

HRID 1373397

Reaction equation

[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:15]([C:16](=O)/[CH:17]=[CH:18]/N(C)C)=[C:11]3[CH:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N+]([O-])([O-])=O.[C:34]1([NH:40][C:41]([NH2:43])=[NH2+:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(=O)([O-])[O-].[K+].[K+].CCOCC>CN(C)C=O.O>[NH:40]([C:41]1[N:43]=[C:16]([C:15]2[C:14]([C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)=[N:13][N:12]3[C:7]([NH:6][CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)=[CH:8][CH:9]=[CH:10][C:11]=23)[CH:17]=[CH:18][N:42]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of (2E)-1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-3-(dimethylamino)-2-propen-1-one (100 mg, 0.25 mmol) in N,N-dimethylformamide (5 mL) was added N-phenylguanidinium nitrate (252 mg, 1.27 mmol) and potassium carbonate (175 mg, 1.27 mmol). The suspension was heated at 140° C. (bath temperature) for 21 hours. The mixture was cooled to room temperature, ether was added followed by water. The organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (2:1 hexanes-ethyl acetate) provided 3-(2-anilino-4-pyrimidinyl)-N-cyclopentyl-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-7-amine which was recrystallized from ether/hexanes (90 mg, 76%) to give a white crystalline solid. 1H NMR (CDCl3): δ 8.15 (d, 1 H), 7.69–7.59 (m, 5 H), 7.32–7.27 (m, 3 H), 7.18–7.13 (m, 3 H), 7.02 (t, 1 H), 6.49 (d, 1 H), 6.06–6.01 (m, 2 H), 4.01 (m, 1 H), 2.20–2.10 (m, 2 H), 1.86–1.64 (m, 6 H); 13C NMR (CDCl3): δ 163.20 (d, JCF=246.6 Hz), 161.55, 160.11, 156.76, 152.27, 142.72, 141.15, 139.74, 131.47 (d, JCF=8.3 Hz), 129.72 (d, JCF=3.4 Hz), 128.82, 128.66, 122.28, 119.52, 115.60 (d, JCF=21.3 Hz), 110.83, 106.91, 105.15, 90.34, 53.86, 33.32, 24.05; MS m/z 465 (M+1).

Workup

temperatureThe mixture was cooled to room temperature
washThe organic layer was washed with brine
extractionThe aqueous layer was extracted with ether
dry with materialthe combined organics were dried over magnesium sulfate
filtrationFiltration and concentration

Sources & evidence

ORD record: ord-8f8fdd99d5094949acae264c3a1c2dc5
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07160897B2

Linked notes

Loading…