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

HRID 1262079Notes

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

Participants

Conditions

Temperature: 170 °C

Procedure

A mixture of 2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamine (1.25 g, 0.00411 mol) (for preparation see: Ahmed, et al. WO2008051547), 7-Bromo-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazine (0.75 g, 0.0029 mol) and N,N-Diisopropylethylamine (2.02 mL, 0.0116 mol) in 2-Methoxyethanol (10 mL) was heated in the microwave at 170° C. for 90 minutes. Purification by Isco chromatography gave (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-{2-methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-amine as a tan solid (0.50 g, 35%). MP: 171-173° C.; LCMS (m/e) 500 (M); 1H-NMR (DMSO-d6, 400 MHz) δ 8.83 (s, 1H), 8.02-8.00 (d, 1H, J=8.76 Hz), 7.74 (s, 1H), 6.93-6.85 (q, 2H, J=4.76 Hz), 6.67-6.66 (s, 1H), 6.52-6.49 (d, 1H, J=6.40 Hz), 3.85 (s, 3H), 3.71-3.68 (d, 2H, J=12.20 Hz), 2.67-2.62 (t, 2H, J=11.80 Hz), 2.31-2.28 (br, 4H), 1.83 (s3H), 1.86-1.83 (d, 2H), 1.55-1.50 (2, 2H).

Workup

customPurification by Isco chromatography

Sources & evidence

ORD record: ord-e8507800bf144b8dbae7fe87bfc35538
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08471005B2

Reaction notes

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