Sulfuric Acid → N-[2-({6-[2-Amino-1-(2,6-dichlorophenyl)-2-oxoethyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide

HRID 2096250노트

반응식

HRID 2096250 반응식
[C:1]([CH:3]([C:34]1[C:39]([Cl:40])=[CH:38][CH:37]=[CH:36][C:35]=1[Cl:41])[C:4]1[N:9]=[N:8][C:7]([S:10][C:11]2[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=2[CH2:13][NH:14][C:15](=[O:29])[C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:19]=[C:18]([F:28])[CH:17]=2)=[CH:6][CH:5]=1)#[N:2].S(=O)(=O)(O)[OH:43]>>[NH2:2][C:1](=[O:43])[CH:3]([C:4]1[N:9]=[N:8][C:7]([S:10][C:11]2[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=2[CH2:13][NH:14][C:15](=[O:29])[C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:19]=[C:18]([F:28])[CH:17]=2)=[CH:6][CH:5]=1)[C:34]1[C:35]([Cl:41])=[CH:36][CH:37]=[CH:38][C:39]=1[Cl:40]

참가 물질

3

반응물 2

HCID 1118Sulfuric AcidHCID 66822461N-[2-({6-[Cyano(2,6-dichlorophenyl)methyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide

생성물 1

HCID 46861613N-[2-({6-[2-Amino-1-(2,6-dichlorophenyl)-2-oxoethyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide수율 67%

반응 조건

온도
70 °C

실험 절차

N-[2-({6-[Cyano(2,6-dichlorophenyl)methyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide (92 mg, 0.15 mmol) was treated with concentrated sulfuric acid (2 mL) and the mixture was stirred at 70° C. for 30 min. The solution was cooled to RT, quenched with ice-water and extracted into DCM. The organic layer was washed with aqueous saturated NaHCO3, dried over MgSO4, filtered, and the filtrate was concentrated in vacuo. Purification by flash column chromatography (DCM:MeOH from 97.3:2.7 to 95:5) afforded the title compound (63 mg, 67%) which co-exists in solution as a mixture of the amide and the enol-amine. LCMS (Method 3): Rt 10.15 & 11.27 min, m/z 626 [MH−]. 1H NMR (400 MHz, CD3OD) (ratio amide/enol-amine 1:0.8): 7.65 (1H, dd, J 7.6, 1.2), 7.57-7.43 (5.4H, m), 7.42-7.37 (3.6H, m), 7.36-7.29 (3.6H, m), 7.21 (0.8H, t, J 1.8), 7.17-7.13 (2H, m), 6.99 (0.8H, ddd, J 9, 2.3, 1.4), 6.95-6.93 (1H, m), 6.85-6.80 (1.8H, m), 6.58 (0.8H, d, J 9.9), 6.15 (0.8H, d, J 9.9), 5.98 (1H, s), 4.73 (1.6H, s), 4.71 (2H, d, J 1.8), 3.82 (7.2H, t, J 4.8), 3.22-3.17 (7.2H, m).

후처리

  1. temperatureThe solution was cooled to RT
  2. customquenched with ice-water
  3. extractionextracted into DCM
  4. washThe organic layer was washed with aqueous saturated NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification by flash column chromatography (DCM:MeOH from 97.3:2.7 to 95:5)

출처 및 근거

ORD 기록
ord-774a98110f6344b29d3c3351f617d2f0
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450314B2

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