Toluene → 7-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine

HRID 1369438노트

반응식

HRID 1369438 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[CH3:18][N:19]1[C:23]([CH2:24][OH:25])=[N:22][CH:21]=[N:20]1.[Br:26][C:27]1[C:32](Cl)=[N:31][N:30]2[C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[F:43])=[N:35][N:36]=[C:29]2[CH:28]=1>C1COCC1.[Cl-].[NH4+]>[Br:26][C:27]1[C:32]([O:25][CH2:24][C:23]2[N:19]([CH3:18])[N:20]=[CH:21][N:22]=2)=[N:31][N:30]2[C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[F:43])=[N:35][N:36]=[C:29]2[CH:28]=1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanolHCID 154861767-Bromo-6-chloro-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine

생성물 1

HCID 154861777-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine수율 52%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 25517Ammonium Chloride용매

반응 조건

온도
0 °C

실험 절차

A solution of potassium bis(trimethylsilyl)amide in toluene (16.8 ml, 0.5M, 8.4 mmol) was added to a stirred solution of (2-methyl-2H-1,2,4-triazol-3-yl)methanol (0.95 g, 8.4 mmol) in anhydrous THF (30 ml) at room temperature under nitrogen. After 20 min the suspension was cooled to 0° C. and a suspension of 7-bromo-6-chloro-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (2.28 g, 6.96 mmol) in anhydrous THF (100 ml) was added dropwise. The mixture was stirred for 3 h at 0° C. then poured into ice-water (400 ml), diluted with saturated aqueous ammonium chloride (100 ml) and extracted with dichloromethane-methanol (9:1, 3×100 ml). The extracts were dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica gel, eluting with 3% methanol-dichloromethane, gave 7-bromo-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (1.45 g, 52%) as a yellow solid; 1H NMR (360 MHz, CDCl3) δ3.95 (3H, s), 5.54 (2H, s), 7.28 (1H, dd, J=10 and 10 Hz), 7.37 (1H, ddd, J=8, 8 and 1 Hz), 7.57-7.63 (1H, m), 7.86 (1H, ddd, J=8, 8 and 2 Hz), 7.90 (1H, s), 8.41 (1H, s); MS (ES+) m/e 404/406 [MH]+.

후처리

  1. additionwas added dropwise
  2. extractionextracted with dichloromethane-methanol (9:1, 3×100 ml)
  3. dry with materialThe extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washFlash column chromatography on silica gel, eluting with 3% methanol-dichloromethane

출처 및 근거

ORD 기록
ord-dc6faa2fa1a6445281583a775e3f904a
출처 데이터셋
uspto-grants-2003_06
특허 번호
US06579875B1

반응 노트

불러오는 중…