Acetic Acid → 2-(3,4-Dimethoxy-phenyl)-5-[6-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-pyridin-3-yl]-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409560ノート

反応式

HRID 2409560 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([C:19]4[CH:20]=[N:21][C:22]([N:29]5[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]5)=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH3:35]CN(CC)CC.C=O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([C:19]4[CH:20]=[N:21][C:22]([N:29]5[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]5)=[C:23]([C:25]([F:27])([F:28])[F:26])[CH:24]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

参加物

7

反応物 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 667169522-(3,4-Dimethoxy-phenyl)-5-(6-piperazin-1-yl-5-trifluoromethyl-pyridin-3-yl)-imidazo[2,1-b][1,3,4]thiadiazole

生成物 1

HCID 667169812-(3,4-Dimethoxy-phenyl)-5-[6-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-pyridin-3-yl]-imidazo[2,1-b][1,3,4]thiadiazole収率 50%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a mixture of 2-(3,4-Dimethoxy-phenyl)-5-(6-piperazin-1-yl-5-trifluoromethyl-pyridin-3-yl)-imidazo[2,1-b][1,3,4]thiadiazole (105 mg, 0.199 mmol, 1 eq), Et3N (0.056 mL, 0.399 mmol, 2 eq), formaldehyde (0.180 mL, 2.39 mmol, 12 eq) and acetic acid (0.02 mL, 0.239 mmol, 1.2 eq) in MeOH (4 mL) was added Sodium cyanoborohydride (0.175 g, 2.79 mmol, 14 eq). The reaction mixture was stirred at rt for 2 h. Solvents were evaporated to dryness and the residue was dissolved in sat NaHCO3/EtOAc. Layers were separated and the aqueous layer was extracted once with EtOAc. The combined organic layers were dried, filtered and evaporated. The residue was purified on silica gel (isolute flash Si II, 10 g, 96:4 DCM/7N NH3 in MeOH) to give the desired product (50 mg, 50%). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=3.47 min, [M+H]+ m/z 505.3; 1H NMR (300 MHz, CDCl3) δ 8.92 (s, 1H), 8.49 (d, J=1.9 Hz, 1H), 7.52 (s, 1H), 7.42 (d, J=1.7 Hz, 1H), 7.36 (dd, J=8.3, 2.0 Hz, 1H), 6.90 (d, J=8.4 Hz, 1H), 3.94 (s, 3H), 3.88 (s, 3H), 3.41 (m, 4H), 2.57 (m, 4H), 2.34 (s, 3H).

後処理

  1. customSolvents were evaporated to dryness
  2. dissolutionthe residue was dissolved in sat NaHCO3/EtOAc
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted once with EtOAc
  5. customThe combined organic layers were dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified on silica gel (isolute flash Si II, 10 g, 96:4 DCM/7N NH3 in MeOH)

出典と根拠

ORDレコード
ord-4bb1b2355f9849cdbea039877918f2cf
出典データセット
uspto-grants-2014_08
特許番号
US08815918B2

反応ノート

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