Hydrazine hydrate (1:1) → 8-(4-Fluorophenyl)-9-(1-methyl-1H-imidazo[4,5-c]pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 1467704Notes

Reaction equation

HRID 1467704 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:17]([C:18]3[N:19]([CH3:27])[C:20]4[CH:25]=[CH:24][N:23]=[CH:22][C:21]=4[N:26]=3)[C:16](=O)[C:15]3[C:14]([C:29]([O:31]CC)=O)=[CH:13][CH:12]=[CH:11][C:10]=3[NH:9]2)=[CH:4][CH:3]=1.O.[NH2:35][NH2:36]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[NH:9][C:10]3[C:15]4[C:16](=[N:35][NH:36][C:29](=[O:31])[C:14]=4[CH:13]=[CH:12][CH:11]=3)[CH:17]2[C:18]2[N:19]([CH3:27])[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][C:21]=3[N:26]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67261937Ethyl 2-(4-fluorophenyl)-3-(1-methyl-1H-imidazo[4,5-c]pyridin-2-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

Product 1

HCID 1362651738-(4-Fluorophenyl)-9-(1-methyl-1H-imidazo[4,5-c]pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The mixture of ethyl 2-(4-fluorophenyl)-3-(1-methyl-1H-imidazo[4,5-c]pyridin-2-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (150 mg, 0.34 mmol) and hydrazine monohydrate (2 mL) in methanol (5 mL) was stirred at room temperature for 4 h. Then methanol was evaporated under reduced pressure and the residue was extracted with ethyl acetate (20 mL×4). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to give crude product, which was purified by chromatography (silica gel, DCM/MeOH=25:1 to 1:1) to give the title compound (6.7 mg, yield 5%). LC-MS (ESI) m/z: 413 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 3.58 (s, 3H), 4.93-4.95 (d, J=11.6 Hz, 1H), 5.04-5.07 (d, J=11.6 Hz, 1H), 6.85-6.90 (t, J=8.8 Hz, 2H), 7.12-7.14 (d, J=8.0 Hz, 1H), 7.38-7.44 (m, 3H), 7.49-7.57 (m, 2H), 8.19-8.21 (d, J=5.6 Hz, 1H), 8.72 (s, 1H).

Workup

  1. customThen methanol was evaporated under reduced pressure
  2. extractionthe residue was extracted with ethyl acetate (20 mL×4)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give crude product, which
  7. customwas purified by chromatography (silica gel, DCM/MeOH=25:1 to 1:1)

Sources & evidence

ORD record
ord-2aa26454b884483aa1afb65cbd7928d0
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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