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 1888577Notes

Reaction equation

HRID 1888577 reaction equation
[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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-1aecaa40039d4c82b9d2b8c9612e2454
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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