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 1506039노트

반응식

HRID 1506039 반응식
[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

참가 물질

9

반응물 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 123421,2-HydrazinedicarboxaldehydeHCID 58266504HCID 58266504, 화합물

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매2회HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c8500b6e6b4549c49dbbd36d83bbf02b
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216980B2

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