Pyridine → 3-fluoro-N-[2-amino-4-(4-methyl-1-piperazinyl)-phenyl]benzenesulfonamide

HRID 346717

반응식

HRID 346717 반응식
[F:1][C:2]1[CH:3]=[C:4]([S:8](Cl)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)=[CH:16][C:14]=1[NH2:15].N1C=CC=CC=1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([S:8]([NH:12][C:13]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25]3)=[CH:16][C:14]=2[NH2:15])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 1049PyridineHCID 27342583-Fluorobenzenesulfonyl ChlorideHCID 27635454-(4-Methylpiperazino)-1,2-benzenediamine

생성물 1

HCID 222724783-fluoro-N-[2-amino-4-(4-methyl-1-piperazinyl)-phenyl]benzenesulfonamide수율 57%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 2-nitro-3-chloroaniline (4.47 g, 25.9 mmol), methylpiperazine (3.1 g, 31 mmol) and K2CO3 (5.41 g, 39 mmol) in acetonitrile was stirred at 70° C. for 48 h. The mixture was filtered and purified by column chromatography (SiO2, CH2Cl2/MeOH/Heptane/NH3 4:1:5×0.2%) to give 1.6 g of product (unreacted starting material was isolated): 1H-NMR δ 7.66–7.45 (m, 5H), 6.78 (d, 1H), 6.62 (d, 1H), 6.50 (dd, 1H), 3.39–3.35 (m, 4H), 3.02-2.99 (m, 4H); MS (posES-FIA) m/z 333.0 (M++H). The product (1.06 g, 4.49 mmol) was dissolved in EtOH:THF (4:1). Raney-Ni and hydrazine (1.12 mL, 22 mmol) were added. The reaction was stirred at room temperature for 3 h until the yellow color disappeared. Filtration through wet Celite pad, followed by removal of the solvent afforded 0.802 g of 2-amino-5-(4-methyl-1-piperazinyl)aniline which was used without further purification in the next step. 3-Fluorobenzenesulfonyl chloride (0.133 g, 0.68 mmol) was added to a solution of 2-amino-5-(4-methyl-1-piperazinyl)aniline (0.141 g, 0.68 mmol) and pyridine (514 mL, 6.39 mmol) in CH2Cl2. After 1 h the mixture was washed with aq NaHCO3 (10%), dried (MgSO4) and the solvent was removed. Purification by chromatography (SiO2, CH2Cl2/methanol/heptane, 4:1:5) gave 3-fluoro-N-[2-amino-4-(4-methyl-1-piperazinyl)-phenyl]benzenesulfonamide (0.140 g, 57%). MS (posES-FIA) m/z=found: 365.2, calcd: 364.14; Anal. (C17H22ClFN4O2S.3H2O) C, H, N, S. The reaction produced a small amount of bis-sulfonylated compound 3-fluoro-N-[2-{[(3-fluorophenyl)sulfonyl]amino}-4-(4-methyl-1-piperazinyl)-phenyl]be (0.010 g, 3%). The products were transformed into their HCl-salt before analysis; MS (posES-FIA) m/z=found. 523.5, calcd: 522.12. Anal. (C23H25ClF2N4O4S2) C, H, N, S.

후처리

  1. customwas used without further purification in the next step
  2. washAfter 1 h the mixture was washed with aq NaHCO3 (10%)
  3. dry with materialdried (MgSO4)
  4. customthe solvent was removed
  5. customPurification by chromatography (SiO2, CH2Cl2/methanol/heptane, 4:1:5)

출처 및 근거

ORD 기록
ord-89c414d7c4d643ec8e8a9b2c549bb277
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173035B2

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