Water → 2-(2-{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-N,N-dimethyl-benzenesulfonamide

HRID 1262080Notes

Reaction equation

HRID 1262080 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][CH:21]([N:24]5[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]5)[CH2:20][CH2:19]4)=[CH:14][C:13]=3[O:31][CH3:32])=[N:9]2)=[CH:4][CH:3]=1.[CH3:33][N:34]([CH3:38])[SH:35](=[O:37])=[O:36].[CH:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCCC1.C(O)C.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:13]1[CH:14]=[C:15]([N:18]2[CH2:19][CH2:20][CH:21]([N:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)[CH2:22][CH2:23]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:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[S:35]([N:34]([CH3:38])[CH3:33])(=[O:37])=[O:36])[N:10]2[N:9]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 66711255(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}-amineHCID 178486094HCID 178486094, compound

Product 1

HCID 667112502-(2-{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-N,N-dimethyl-benzenesulfonamideYield 48%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (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 (0.09 g, 0.0002 mol) and N,N-dimethylsulfonamide-2-benzeneboronic acid (0.060 g, 0.00026 mol), Tetrakis(triphenylphosphine)palladium(0) (0.023 g, 0.000020 mol), 1 M of Sodium carbonate in Water (0.7 mL, 0.0007 mol), Tetrahydrofuran (4 mL,) and ethanol (4 mL) under nitrogen was heated at 80° C. overnight. Purification by prep plate chromatography gave 2-(2-{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-N,N-dimethyl-benzenesulfonamide (0.052 g, 48%) as a tan solid. MP; 198-205° C.; 1H-NMR (DMSO-d6, 400 MHz) δ 8.91 (s, 1H), 8.04-8.02 (d, 1H, J=7.80 Hz), 7.81-7.79 (t, 1H, J=7.44 Hz), 7.77-7.75 (t, 1H, J=7.56 Hz), 7.65-7.63 (d, 1H, J=7.48 Hz), 7.53-7.51 (d, 1H, J=8.76 Hz), 7.46 (s, 1H), 6.91-6.86 (q, 1H, J=4.56 Hz), 6.58-6.57 (d, 1H, J=2.40 Hz), 6.16-6.13 (d, 1H, J=12.44 Hz), 3.80 (s, 3H), 3.60-3.56 (d, 2H, J=12.44 Hz), 2.35 (s, 6H), 2.17 (s, 3H), 1.83-1.80 (d, 2H, J=11.88 Hz), 1.49-1.46 (q, 2H, J=8.52 Hz) 1.23 (s, 1H).

Workup

  1. customPurification by prep plate chromatography

Sources & evidence

ORD record
ord-9be75a77a65841eb8f0b2fedf9361c47
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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