Dimethylformamide → 7-(2-Methoxy-phenyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile

HRID 1261907Notes

Reaction equation

HRID 1261907 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])[N:5]2[C:10]=1[CH:9]=[N:8][C:7]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][CH:13]=1)=[N:6]2.[CH3:33][N:34](C)C=O>[C-]#N.[Zn+2].[C-]#N.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:32][O:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:4]1[N:5]2[C:10]([CH:9]=[N:8][C:7]([NH:11][C:12]3[CH:13]=[CH:14][C:15]([N:18]4[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]4)=[CH:16][CH:17]=3)=[N:6]2)=[C:2]([C:33]#[N:34])[CH:3]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 66711068[5-Bromo-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 667112217-(2-Methoxy-phenyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

Into a Microwave vial, [5-Bromo-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.151 g, 0.000306 mol), Zinc Cyanide (0.0719 g, 0.000612 mol), Copper(I) iodide (5.8 mg, 0.000031 mol) and Tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.000031 mol) were added and purged with nitrogen for 10 minutes. N,N-Dimethylformamide (3.00 mL, 0.0387 mol) was added. The reaction was microwaved on 300 watts, 150° C. for 60 minutes. The solvent was removed under vacuum. The reaction was purified via ISCO column chromatography with DCM and MeOH as eluant (0 to 10% methanol). The collected fractions afforded 7-(2-Methoxy-phenyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile a yellow solid (62 mg, 46%). LCMS (E/I+) 440.18M+H). NMR 1H (DSMO-d6)-9.59 (s, 1H), 9.20 (s, 1H), 7.72 (dd, 1H, J=1.64, 6.00 Hz), 7.46-7.57 (m, 3H), 7.43 (s, 1H), 7.42 (d, 1H, J=8.33 Hz), 7.13 (t, 1H, J=7.56 Hz), 6.80 (d, 2H, J=9.13 Hz), 3.79 (s, 3H), 3.04 (t, 4H, J=4.64, 2.43 (t, 4H, J=4.84), 2.21 (s, 3H).

Workup

  1. custompurged with nitrogen for 10 minutes
  2. customThe reaction was microwaved on 300 watts, 150° C. for 60 minutes
  3. customThe solvent was removed under vacuum
  4. customThe reaction was purified via ISCO column chromatography with DCM and MeOH as eluant (0 to 10% methanol)

Sources & evidence

ORD record
ord-fb8a3ce690b64fbf8a168d379298ce99
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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