[7-(2-Methoxy-phenyl)-5-vinyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine → [5-Ethyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1261903Notes

Reaction equation

HRID 1261903 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:17]2[C:12]([CH:13]=[N:14][C:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)=[CH:21][CH:20]=3)=[N:16]2)=[C:11]([CH:32]=[CH2:33])[CH:10]=1>C(O)C.[Ni]>[CH2:32]([C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[N:17]2[C:12]=1[CH:13]=[N:14][C:15]([NH:18][C:19]1[CH:20]=[CH:21][C:22]([N:25]3[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]3)=[CH:23][CH:24]=1)=[N:16]2)[CH3:33]

Participants

4

Reactant 1

HCID 66711513[7-(2-Methoxy-phenyl)-5-vinyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66711526[5-Ethyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amineYield 36%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent2×

Procedure

Into a par bottle, [7-(2-Methoxy-phenyl)-5-vinyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (50.00 mg, 0.0001135 mol), and Ethanol (20 mL, 0.3 mol) were added. Raney-Nickel (0.9:0.1, Nickel:Aluminum, 10 mg, 0.0002 mol) was washed with Ethanol prior to adding to the reaction mixture. The mixture was evacuated and charged with hydrogen at 30 pSi. The reaction was shaken on the parr at 30 pSi for one hour. The solid was filtered through Celite. The organic was evaporated under vacuum to give a yellow solid. The solid was purified via ISCO column chromatography with DCM and MeOH as eluant (0 to 10% methanol). The collected fractions afforded [5-Ethyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine as a yellow solid (18 mg, 36%). MP 154-156° C. LCMS (E/I+) 443.31 (M+H). NMR 1H (DSMO-d6)-9.05 (s, 1H), 8.92 (s, 1H), 7.80 (dd, 1H, JJ=1.57, 6.50 Hz), 7.55 (d, 2H, J=8.96 Hz), 7.43 (dt, 1H, JJ=1.60, 7.00 Hz), 7.20 (d, 1H, J=8.40) 7.10 (t, 1H, J=7.57 Hz, 6.73-6.85 (m, 3H), 3.79 (s, 3H), 3.02 (t, 4H, J=4.60), 2.83 (q, 2H, JJ=7.52, 7.56 Hz), 2.44 (t, 4H, J=5.84), 2.21 (s, 3H), 1.28 (t, 3H, J=7.56 Hz).

Workup

  1. additionto adding to the reaction mixture
  2. customThe mixture was evacuated
  3. additioncharged with hydrogen at 30 pSi
  4. filtrationThe solid was filtered through Celite
  5. customThe organic was evaporated under vacuum
  6. customto give a yellow solid
  7. customThe solid was purified via ISCO column chromatography with DCM and MeOH as eluant (0 to 10% methanol)

Sources & evidence

ORD record
ord-430d19be568e4686be60a5ff0fe6bd13
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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