N-methyl-2-pyrrolidone → [2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-[7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

HRID 1261885Notes

Reaction equation

HRID 1261885 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][C:13]=3[O:25][CH3:26])=[N:9]2)=[CH:4][CH:3]=1.[CH3:27][O:28][C:29]1C=[C:33]([N:35]2CCN(C)CC2)[CH:32]=[CH:31][C:30]=1N.BrC1N2C(C=NC(S(C)=O)=N2)=CC=1.CN1CCCC1=O>>[CH3:26][O:25][C:13]1[CH:14]=[C:15]([N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[CH:16]=[CH:17][C:12]=1[NH:11][C:8]1[N:7]=[CH:6][C:5]2=[CH:4][CH:3]=[C:2]([C:32]3[CH:33]=[N:35][C:29]([O:28][CH3:27])=[CH:30][CH:31]=3)[N:10]2[N:9]=1

Participants

5

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 201362532-Methoxy-4-(4-methylpiperazin-1-yl)anilineHCID 580713077-Bromo-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazineHCID 66710919(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66711356[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-[7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

Conditions

Temperature
145 °C

Procedure

(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine: Into a 30 mL vial, [A] 2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamine (1.08 g, 0.00490 mol), [B] 7-Bromo-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazine (0.580 g, 0.00223 mol) and N-Methylpyrrolidinone (3.50 mL, 0.0363 mol) were added. The reaction mixture was heated at 145° C. for 2.5 hours. The solvent was removed under vacuum to give a solid. The solid was partitioned with water and DCM. The organic was separated, washed with Brine and dried over sodium sulfate. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The desired product was isolated via ISCO column chromatography with DCM and MeOH as eluant (3 to 10% methanol). The collected fractions afforded (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine as a yellow solid (0.58 g, 62%). NMR 1H (DSMO-d6)-8.83 (s, 1H), 8.03 (d, 1H, J=8.76 Hz), 7.75 (s, 1H), 6.92 (d, 1H, J=4.58 Hz), 6.86 (d, 1H, J=4.68 Hz), 6.67 (d, 1H, J=2.24 Hz), 6.49 (dd, 1H, JJ=2.32, 6.44 Hz), 3.85 (s, 3H), 3.12 (t, 4H, J=4.64 Hz), 2.46 (t, 4H, J=4.84 Hz), 2.22 (s, 3H)

Workup

  1. customThe solvent was removed under vacuum
  2. customto give a solid
  3. customThe solid was partitioned with water and DCM
  4. customThe organic was separated
  5. washwashed with Brine
  6. dry with materialdried over sodium sulfate
  7. filtrationThe solid was filtered
  8. washwashed with DCM
  9. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-a80237c0528a4e8a9b025c7069c8e648
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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