Tetrahydrofuran → 1-[4-(4-Isobutylamino-imidazo[1,2-a]quinoxalin-1-yl)-phenyl]-3-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-urea

HRID 1025482Notes

Reaction equation

HRID 1025482 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22](B4OC(C)(C)C(C)(C)O4)=[CH:21][CH:20]=3)=[O:17])=[CH:11][C:10]=2[C:34]([F:37])([F:36])[F:35])[CH2:4][CH2:3]1.C1COCC1.Br[C:44]1[N:48]2[C:49]3[C:54]([N:55]=[C:56]([NH:57][CH2:58][CH:59]([CH3:61])[CH3:60])[C:47]2=[N:46][CH:45]=1)=[CH:53][CH:52]=[CH:51][CH:50]=3.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(=O)([O-])[O-].[K+].[K+].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:58]([NH:57][C:56]1[C:47]2[N:48]([C:44]([C:22]3[CH:21]=[CH:20][C:19]([NH:18][C:16]([NH:15][C:12]4[CH:13]=[CH:14][C:9]([CH2:8][N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[C:10]([C:34]([F:35])([F:36])[F:37])[CH:11]=4)=[O:17])=[CH:24][CH:23]=3)=[CH:45][N:46]=2)[C:49]2[C:54]([N:55]=1)=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:59]([CH3:61])[CH3:60]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 80271Tri-o-tolylphosphineHCID 666013371-[4-(4-Methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ureaHCID 66601580(1-Bromo-imidazo[1,2-a]quinoxalin-4-yl)isobutyl-amine

Product 1

HCID 498004231-[4-(4-Isobutylamino-imidazo[1,2-a]quinoxalin-1-yl)-phenyl]-3-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-ureaYield 16.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
140 °C

Procedure

1-[4-(4-Methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-urea (244 mg, 0.47 mmol) was dissolved in potassium carbonate (1.41 mL, 1M in water) and THF (1 mL) and stirred overnight at rt in a sealed vial. (1-bromo-imidazo[1,2-a]quinoxalin-4-yl)-isobutyl-amine (75 mg, 0.235 mmol), Pd(OAc)2 (10.6 mg, 0.047 mmol) and P(oTol)3 (28.6 mg, 0.094 mmol) were added and the mixture was heated at 140° C. under microwave irradiation for 40 min. After cooling, the solution was filtered and subjected to preparative HPLC to give 1-[4-(4-isobutylamino-imidazo[1,2-a]quinoxalin-1-yl)-phenyl]-3-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-urea (24.8 mg, 14%): 1H-NMR (300 MHz, d6-DMSO): δ=9.30 (1H, s), 9.24 (1H, s), 7.98 (1H, s), 7.68-7.50 (6H, m), 7.47 (3H, m), 7.27 (2H, m), 6.93 (1H, dd), 3.51 (2H, s), 3.37 (2H, dd), 2.38 (8H, br s), 2.19 (3H, s), 2.09 (1H, sept), 0.91 (6H, d) ppm; UPLC-MS: RT=1.03 min; m/z (ES+) 631.7 [MH+]; required MW=630.7.

Workup

  1. temperatureAfter cooling
  2. filtrationthe solution was filtered

Sources & evidence

ORD record
ord-6d478fa4345341b6b0ff4558e4e78960
Source dataset
uspto-grants-2014_05
Patent number
US08729082B2

Reaction notes

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