Chlorotrimethylsilane → 3-(4-piperidin-1-ylmethyl-phenyl)-6-(4H-1,2,4-triazol-4-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1506039ノート

反応式

HRID 1506039 の反応式
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:28]([NH:30][NH:31][CH:32]=O)=O.Cl[Si](C)(C)C.C(N(CC)CC)C>N1C=CC=CC=1.O.C(Cl)Cl.CO>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([N:25]6[CH:32]=[N:31][N:30]=[CH:28]6)=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

9

反応物 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 123421,2-HydrazinedicarboxaldehydeHCID 58266504HCID 58266504、化合物

生成物 1

HCID 582663293-(4-piperidin-1-ylmethyl-phenyl)-6-(4H-1,2,4-triazol-4-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole収率 82.2%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒2 回HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (22.3 mg, 62.4 μmol), 1,2-diformylhydrazine (16.5 mg, 0.187 mmol), chloro-trimethylsilane (119 μL, 0.936 mmol) in triethylamine (60.9 μL, 0.437 mmol) and pyridine (340 μL) was heated under reflux for 30 minutes. The cooled reaction mixture was diluted with water, DCM, methanol and water. The layers were separated; the aqueous phase extracted with 20% MeOH in DCM, and the combined organic phase was concentrated in vacuo. The resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min) to afford the title compound as a yellow solid (21 mg, 81%). 1H NMR (DMSO-D6, 400 MHz): 12.50 (s, 1H), 9.25 (s, 2H), 8.99 (d, J=2.1 Hz, 1H), 8.94 (d, J=2.2 Hz, 1H), 8.86 (s, 1H), 8.73 (s, 1H), 7.76 (d, J=8.1 Hz, 2H), 7.46 (d, J=8.1 HZ, 2H), 3.50 (s, 2H), 2.35 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H). LCMS (Method D): RT=7.46 min, M+H+=410.

後処理

  1. temperaturewas heated
  2. temperatureunder reflux for 30 minutes
  3. customThe cooled reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous phase extracted with 20% MeOH in DCM
  6. concentrationthe combined organic phase was concentrated in vacuo
  7. customThe resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min)

出典と根拠

ORDレコード
ord-c8500b6e6b4549c49dbbd36d83bbf02b
出典データセット
uspto-grants-2015_12
特許番号
US09216980B2

反応ノート

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