Triethylamine → N-Methyl-N-(3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzyl)-methanesulfonamide

HRID 1262202Notes

Reaction equation

HRID 1262202 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[N:20]=[CH:19][C:18]4=[CH:21][CH:22]=[C:23]([C:24]5[CH:25]=[C:26]([CH2:30]O)[CH:27]=[CH:28][CH:29]=5)[N:17]4[N:16]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.[CH3:49][NH:50][S:51]([CH3:54])(=[O:53])=[O:52].[H-].[Na+]>CN(C)C=O>[CH3:49][N:50]([CH2:30][C:26]1[CH:27]=[CH:28][CH:29]=[C:24]([C:23]2[N:17]3[C:18]([CH:19]=[N:20][C:15]([NH:14][C:11]4[CH:10]=[CH:9][C:8]([N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[CH:13][CH:12]=4)=[N:16]3)=[CH:21][CH:22]=2)[CH:25]=1)[S:51]([CH3:54])(=[O:53])=[O:52]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 85257Methanesulfonate2×HCID 97632N-MethylmethanesulfonamideHCID 66711788(3-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol

Product 1

HCID 66712312N-Methyl-N-(3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzyl)-methanesulfonamideYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(3-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol (63.0 mg, 0.152 mmol) was dissolved in N,N-dimethylformamide (3.00 mL) and triethylamine (27.5 μL, 0.198 mmol). Methanesulfonyl chloride (14.1 μL, 0.182 mmol) was added and the reaction was stirred at room temperature for 40 minutes. LCMS analysis showed complete conversion to the mesylate. In a clean round bottomed flask was added N-methyl-methanesulfonamide (332 mg, 3.04 mmol) in N,N-dimethylformamide (5.00 mL). Sodium hydride (29.2 mg, 1.22 mmol) was added and the reaction was stirred at room temperature for 5 minutes. The mesylate solution was then added and the reaction was stirred at room temperature for 2 hours. The reaction was partitioned between EtOAc (25 mL) and water (25 mL). The organic layer was washed twice with water (15 mL) and dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by prep-HPLC using a gradient of 10-55% AcN/water both containing 0.1% TFA as the eluting solvent. The product was then free based to obtain the title compound as a yellow solid (42 mg, 55%). m.p.=229-230° C.; LCMS (m/e) 506 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.69 (s, 1H), 8.15-8.08 (m, 2H), 7.56-7.46 (m, 3H), 7.38 (d, 1H, J=7.6 Hz), 7.00 (d, 1H, J=4.7 Hz), 6.93 (d, 2H, J=9.0 Hz), 6.82 (d, 1H, J=4.8 Hz), 6.68 (s, 1H), 4.40 (s, 2H), 3.22-3.15 (m, 4H), 2.86 (s, 3H), 2.79 (s, 3H), 2.63-2.56 (m, 4H), 2.37 (s, 3H).

Workup

  1. stirringthe reaction was stirred at room temperature for 5 minutes
  2. stirringthe reaction was stirred at room temperature for 2 hours
  3. customThe reaction was partitioned between EtOAc (25 mL) and water (25 mL)
  4. washThe organic layer was washed twice with water (15 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification

Sources & evidence

ORD record
ord-ce0bd94acb1a4f1eb7398fa4c5384b5a
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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