tert-Butanol → [7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[5-(4-methyl-piperazin-1-yl)-pyridin-2-yl]-amine
Reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:4][CH2:3]1.CS([C:18]1[N:23]=[CH:22][C:21]2=[CH:24][CH:25]=[C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[O:33][CH3:34])[N:20]2[N:19]=1)=O.[F-].[Cs+].C(N(CC)C(C)C)(C)C.C(O)(C)(C)C>>[CH3:34][O:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:26]1[N:20]2[C:21]([CH:22]=[N:23][C:18]([NH:14][C:11]3[CH:10]=[CH:9][C:8]([N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:13][N:12]=3)=[N:19]2)=[CH:24][CH:25]=1Participants
Reactant 5
Product 1
Conditions
- Temperature
- 120 °C
Procedure
Into a 8-dram vial, 5-(4-Methyl-piperazin-1-yl)-pyridin-2-ylamine (0.154 g, 0.804 mmol), 2-Methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (0.105 g, 0.365 mmol), Cesium fluoride (0.139 g, 0.914 mmol), N,N-Diisopropylethylamine (0.1400 mL, 0.8039 mmol) and tert-Butyl alcohol (2.00 mL, 20.9 mmol) were added. The reaction was heated at 120° C. overnight. LCMS suggested presence of desired product. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give [7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[5-(4-methyl-piperazin-1-yl)-pyridin-2-yl]-amine as a yellow solid (30 mg, 22%). LCMS (E/I+) 416.18 (M+H). NMR 1H (DMSO-d6)-9.80 (s, 1H), 9.72 (bs, 1H), 9.01 (s, 1H), 7.99 (s, 1H), 7.90 (d, 1H, J=9.58 Hz), 7.80 (d, 1H, J=7.49), 7.53 (d, 1H, J=9.38 Hz), 7.47 (d, 1H, J=7.59 Hz), 7.24 (d, 1H, J=8.04 Hz), 7.14 (t, 1H, J=7.15 Hz), 7.01 (s, 2H), 3.80 (bs, 5H), 3.55 (d, 2H, J=11.72 Hz), 3.19 (q, 2H, J=10.34 Hz), 2.96 (t, 2H, J=11.72 Hz), 2.83 (s, 3H).
Sources & evidence
- ORD record
- ord-7ea3cf9ee5b1404c9e366fc1139d521e
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08471005B2
Reaction notes
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