2-Methoxyethanol → {2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

HRID 1261967Notes

Reaction equation

HRID 1261967 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]3[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH2:22].CS([C:26]1[N:31]=[CH:30][C:29]2=[CH:32][CH:33]=[C:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][CH3:42])[N:28]2[N:27]=1)=O.C(N(CC)C(C)C)(C)C.COCCO>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]3[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:22][C:26]1[N:31]=[CH:30][C:29]2=[CH:32][CH:33]=[C:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][CH3:42])[N:28]2[N:27]=1

Participants

5

Reactant 4

HCID 80192-MethoxyethanolHCID 81531DiisopropylethylamineHCID 457899912-Methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)anilineHCID 667107912-Methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 54578107{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

Procedure

A solution of 2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamine (0.18 g, 0.00059 mol) with 2-methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (85 mg, 0.30 mol) and N,N-diisopropylethylamine (0.057 g, 0.44 mmol) in 2-methoxyethanol (1.0 mL, 0.013 mol) in a microwave vessel was microwaved on 300 watts, 180° C. for 30 minutes. Repeated microwave for 30 minutes more to get to completion. Filtered through 0.45μ filter and purified by reverse phase HPLC. Concentrated and dissolved in DCM/MeOH and free-based with solid MP-carbonate. Filtered and concentrated {2-methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amineisolated as a brownish film (12 mg, 8%). 1H-NMR (CDCl3) δ 8.69 (s, 1H), 8.24 (d, J=8.8 Hz, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.44 (t, J=8.0, 1H), 7.31 (s, 1H), 7.14 (t, J=7.5, 1H), 7.08 (d, J=8.0, 1H), 7.03 (d, J=4.7 Hz, 1H), 6.83 (d, J=4.6 Hz, 1H), 6.57-6.45 (m, 1H), 6.46-6.43 (m, 1H), 3.89 (s, 3H), 3.62 (s, 3H), 3.64 (broad d, J=12.3 Hz, 2H), 2.72-2.66 (m, 4H), 2.55-2.51 (broad m, 3H), 1.97 (broad d, J=12.4 Hz, 2H), 1.78-1.72 (m, 2H), 1.32-1.20 (m, 2H), 0.94-0.85 (m, 2H); LC/MS (ESI+): 528 (M+H).

Workup

  1. customfor 30 minutes
  2. customto get to completion
  3. filtrationFiltered through 0.45μ
  4. filtrationfilter
  5. custompurified by reverse phase HPLC
  6. concentrationConcentrated
  7. dissolutiondissolved in DCM/MeOH and free-based with solid MP-carbonate
  8. filtrationFiltered

Sources & evidence

ORD record
ord-592c071350ea4ce185d2b183e5278f27
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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