Formaldehyde → 5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl) methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole

HRID 1475188노트

반응식

HRID 1475188 반응식
F[C:2](F)(F)C([O-])=O.[CH3:8][C:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([N:21]3[CH2:26][CH2:25][NH2+:24][CH2:23][CH2:22]3)[CH:16]=2)[N:12]=[C:11]([C:27]2[O:31][N:30]=[C:29]([C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=3)[N:28]=2)[N:10]=1.C=O.[BH3-]C#N.[Na+]>CCO>[CH3:8][C:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([CH3:2])[CH2:23][CH2:22]3)[CH:16]=2)[N:12]=[C:11]([C:27]2[O:31][N:30]=[C:29]([C:32]3[CH:33]=[CH:34][C:35]([O:38][C:39]([F:42])([F:40])[F:41])=[CH:36][CH:37]=3)[N:28]=2)[N:10]=1

참가 물질

5

반응물 3

HCID 712Formaldehyde2회HCID 5003444Sodium cyanoborohydrideHCID 867118804-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium 2,2,2-trifluoroacetate

생성물 1

HCID 732117755-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl) methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole수율 45%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

The mixture of 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium trifluoroacetate (100 mg, 0.2 mmol), formaldehyde (0.5 mL, 6.0 mmol, 38% in H2O) and paraformaldehyde (100 mg, 3.3 mmol) in EtOH (1 mL) was stirred at RT, then treated with NaBH3CN (63 mg, 1.0 mmol) in one portion. The mixture was stirred at RT for 3 h, and then concentrated under reduced pressure to give the crude product, which was purified by pre-HPLC (Mobile phase: A=10 mM NH4HCO3/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge C18, 5 um, 30 mm×150 mm) to afford 5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl) methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole as a white solid (45 mg, 45%). MS (ES+) C23H23F3N8O2 requires: 500. found: 501 [M+H]+; 1H NMR (500 MHz, DMSO-d6) δ 8.22 (d, J=8.3 Hz, 2H), 8.08 (d, J=5.3 Hz, 1H), 7.60 (d, J=8.2 Hz, 2H), 6.77 (s, 1H), 6.42 (d, J=5.3 Hz, 1H), 5.50 (s, 2H), 3.50-3.48 (m, 4H), 2.58 (s, 3H), 2.41-2.32 (m, 4H), 2.20 (s, 3H).

후처리

  1. stirringThe mixture was stirred at RT for 3 h
  2. concentrationconcentrated under reduced pressure
  3. customto give the crude product, which
  4. customwas purified by pre-HPLC (Mobile phase

출처 및 근거

ORD 기록
ord-f39751ccb2bd4ad0848715d52da57f95
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018380B2

반응 노트

불러오는 중…