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 1475188ノート

反応式

HRID 1475188 の反応式
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

参加物

5

反応物 3

HCID 712Formaldehyde2 回HCID 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

生成物 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-oxadiazole収率 45%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f39751ccb2bd4ad0848715d52da57f95
出典データセット
uspto-grants-2015_04
特許番号
US09018380B2

反応ノート

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