Sodium Carbonate → N-(3-(6-(4-(1-Ethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 1363511Notes

Reaction equation

HRID 1363511 reaction equation
O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:14]1[N:15]=[C:16]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[C:34](=[O:35])[NH:33][CH2:32][CH2:31][N:30]3[CH2:36][CH3:37])=[CH:25][CH:24]=2)[C:17](=[O:21])[N:18]([CH3:20])[CH:19]=1.[F:38][C:39]1[C:44]([NH:45][C:46]([C:48]2[S:52][C:51]3[CH2:53][CH2:54][CH2:55][CH2:56][C:50]=3[CH:49]=2)=[O:47])=[C:43]([CH3:57])[C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][CH:40]=1>O>[CH2:36]([N:30]1[CH2:31][CH2:32][NH:33][C:34](=[O:35])[CH:29]1[C:26]1[CH:27]=[CH:28][C:23]([NH:22][C:16]2[C:17](=[O:21])[N:18]([CH3:20])[CH:19]=[C:14]([C:42]3[C:43]([CH3:57])=[C:44]([NH:45][C:46]([C:48]4[S:52][C:51]5[CH2:53][CH2:54][CH2:55][CH2:56][C:50]=5[CH:49]=4)=[O:47])[C:39]([F:38])=[CH:40][CH:41]=3)[N:15]=2)=[CH:24][CH:25]=1)[CH3:37]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 576251865-Bromo-3-(4-(1-ethyl-3-oxopiperazin-2-yl)phenylamino]-1-methylpyrazin-2(1H)-oneHCID 66941485HCID 66941485, compound

Product 1

HCID 25234289N-(3-(6-(4-(1-Ethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideYield 41%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (13 mL), water (3 mL) and sodium carbonate (417 mg, 3.93 mmol). After bubbling nitrogen through the resulting mixture for 15 min, 34 (150 mg, 0.370 mmol), N-(6-Fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydro benzo[b]thiophene-2-carboxamide. (192 mg, 0.460 mmol and tetrakis(triphenyl phosphine)palladium(0) (75 mg, 0.065 mmol) were added, and the reaction mixture then heated at reflux for 5 h. After this time, the reaction mixture was cooled to room temperature, filtered and the filter cake washed with diethyl ether (10 mL). The resulting solid was dissolved in methylene chloride/methanol (10:1), absorbed onto silica gel and purified by flash chromatography to afford 35 in 41% yield (93 mg) as a yellow solid: mp 179-180° C.; 1H NMR (500 MHz, CDCl3) δ 8.31 (bs, 1H), 7.79 (d, 2H, J=8.5 Hz), 7.39 (m, 3H), 7.33 (m, 1H), 7.22 (s, 1H), 7.04 (t, 1H, J=8.0 Hz), 6.68 (s, 1H), 5.80 (d, 1H, J=3.5 Hz), 3.99 (s, 1H), 3.65 (s, 3H), 3.64 (m, 1H), 3.36 (m, 1H), 3.11 (m, 1H), 2.82 (t, 2H, J=6.0 Hz), 2.66 (t, 2H, J=6.0 Hz), 2.59 (m, 2H), 2.36 (s, 3H), 2.27 (m, 1H), 1.85 (m, 4H), 0.99 (t, 3H, J=7.0 Hz); MS (ESI+) m/z 615.3 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser and nitrogen inlet
  3. customAfter bubbling nitrogen through the resulting mixture for 15 min
  4. temperaturethe reaction mixture then heated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. washthe filter cake washed with diethyl ether (10 mL)
  8. dissolutionThe resulting solid was dissolved in methylene chloride/methanol (10:1)
  9. customabsorbed onto silica gel
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-7bce3ff802e9453ca484a991d3a2c93c
Source dataset
uspto-grants-2011_02
Patent number
US07884108B2

Reaction notes

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