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

HRID 1262015Notes

Reaction equation

HRID 1262015 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1.Br[C:26]1[N:34]2[C:29]([CH:30]=[N:31][C:32]([NH:35][C:36]3[CH:41]=[CH:40][C:39]([N:42]4[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]4)=[CH:38][CH:37]=3)=[N:33]2)=[CH:28][CH:27]=1.[CH3:49][NH:50][S:51]([C:54]1[CH:59]=[CH:58][CH:57]=[C:56](B(O)O)[CH:55]=1)(=[O:53])=[O:52].C(=O)([O-])[O-].[Na+].[Na+].O.C(O)C.[Cl-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:49][NH:50][S:51]([C:54]1[CH:55]=[CH:56][CH:57]=[C:58]([C:26]2[N:34]3[C:29]([CH:30]=[N:31][C:32]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([N:42]5[CH2:43][CH2:44][N:45]([CH3:48])[CH2:46][CH2:47]5)=[CH:40][CH:41]=4)=[N:33]3)=[CH:28][CH:27]=2)[CH:59]=1)(=[O:52])=[O:53]

Participants

10

Reactant 8

HCID 702EthanolHCID 962WaterHCID 5234Sodium ChlorideHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 44886921Methyl 3-boronobenzenesulfonamideHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66711491N-Methyl-3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzenesulfonamideYield 24.7%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Palladium Acetate (0.017 g, 0.000077 mol) and Triphenylphosphine (0.025 g, 0.000097 mol) were dissolved in Tetrahydrofuran (1.2 mL, 0.014 mol) and the mixture was allowed to stir at room temperature for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.125 g, 0.000323 mol) was then added and the reaction was again allowed to stir for 10 minutes. N-methyl-3-boronobenzenesulfonamide (0.166 g, 0.000775 mol) was added followed by 0.9 M of Sodium carbonate in water (0.9 mL, 0.0008 mol) and Ethanol (1.2 mL, 0.020 mol). The reaction mixture was then heated at 80° C. and was allowed to stir overnight. The reaction mixture was poured over saturated sodium chloride, and organics were extracted with ethyl acetate. Combined organics were dried over sodium sulfate, filtered and reduced en vacuo. The crude mixture was purified by Gilson prep HPLC to afford 38.12 mg of N-Methyl-3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzenesulfonamide as a lyophilized powder. (M+H)=478.1. 1H NMR (400 MHz, DMSO, d6) δ 9.74 (s, 1H), 9.40 (s, 1H), 9.02 (s, 1H), 8.53 (s, 1H), 8.40 (m, 1H), 7.76 (m, 2H), 7.68 (m, 2H), 7.55 (m, 1H), 7.19 (d, 1H, J=4.28 Hz), 7.04 (m, 1H), 6.98 (d, 1H, J=4.32 Hz), 3.72 (m, 2H), 3.53 (m, 2H), 3.20 (m, 2H), 2.94 (m, 2H), 2.91 (s, 3H), 2.40 (s, 3H).

Workup

  1. stirringto stir for 10 minutes
  2. temperatureThe reaction mixture was then heated at 80° C.
  3. stirringto stir overnight
  4. extractionorganics were extracted with ethyl acetate
  5. dry with materialCombined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. customThe crude mixture was purified by Gilson prep HPLC

Sources & evidence

ORD record
ord-efbe047913b54e91bcac7f5f7750704a
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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