Triphenylphosphine → 3-Methyl-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide

HRID 522528

반응식

HRID 522528 반응식
Br[C:2]1[C:3]([C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:19])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.[C:27]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[Zn]C>C1COCC1.[Pd]>[CH3:27][C:2]1[C:3]([C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:19])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1

참가 물질

6

반응물 3

HCID 11776TriphenylphosphineHCID 866651473-bromo-6-(4-methylsulfonylphenyl)-N-phenyl-pyrazine-2-carboxamideHCID 178477798HCID 178477798, 화합물2회

생성물 1

HCID 545972523-Methyl-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide수율 819.5%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 3-bromo-6-(4-methylsulfonylphenyl)-N-phenyl-pyrazine-2-carboxamide (89.4 mg, 0.1634 mmol) and palladium; triphenylphosphane (9.441 mg, 0.008170 mmol) in THF (1 mL) was treated with chloro(methyl)zinc (490.2 μL of 2 M, 0.9804 mmol) and left to stir for 16 hours at ambient temperature. The reaction was treated with further chloro(methyl)zinc (490.2 μL of 2 M, 0.9804 mmol) and allowed to heat at 60° C. for 7 hours. The mixture was allowed to cool to ambient temperature and concentrated in vacuo. The resultant residue was dissolved in DMSO and purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (24.6 mg, 41% Yield). 1H NMR (400.0 MHz, DMSO) δ 2.81 (s, 3H), 3.31 (s, 3H), 7.15-7.19 (m, 1H), 7.39-7.43 (m, 2H), 7.82 (d, J=7.6 Hz, 2H), 8.11 (d, J=8.5 Hz, 2H), 8.56 (d, J=8.5 Hz, 2H), 9.44 (s, 1H) and 10.71 (s, 1H) ppm; MS (ES+) 367.98. LCMS retention time, 3.37 min.

후처리

  1. waitleft
  2. temperatureto heat at 60° C. for 7 hours
  3. temperatureto cool to ambient temperature
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resultant residue was dissolved in DMSO
  6. custompurified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  7. customThe fractions were collected
  8. customfreeze-dried

출처 및 근거

ORD 기록
ord-ce35615e860b44ea856f2cfcdfb82425
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334244B2

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