Hydrazine hydrate (1:1) → 8-(4-((Dimethylamino)methyl)phenyl)-5-fluoro-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 907977Notes

Reaction equation

HRID 907977 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH:20]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[C:19](=O)[C:18]3[C:17]([C:29](OCC)=O)=[CH:16][C:15]([F:34])=[CH:14][C:13]=3[NH:12]2)=[CH:7][CH:6]=1)[CH3:3].[OH2:35].[NH2:36][NH2:37]>CO>[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([CH:11]2[NH:12][C:13]3[C:18]4[C:19](=[N:36][NH:37][C:29](=[O:35])[C:17]=4[CH:16]=[C:15]([F:34])[CH:14]=3)[CH:20]2[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[CH:9][CH:10]=1)[CH3:3]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67261296Ethyl 2-(4-((dimethylamino)methyl)phenyl)-7-fluoro-3-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

Product 1

HCID 1361863108-(4-((Dimethylamino)methyl)phenyl)-5-fluoro-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 37%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of ethyl 2-(4-((dimethylamino)methyl)phenyl)-7-fluoro-3-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (100 mg) in 85% hydrazine monohydrate (0.5 mL) and methanol (2 mL) was stirred at room temperature overnight. Methanol was removed under reduced pressure. The crude was purified by prep-HPLC to give the title compound (35 mg, yield 37%). LC-MS (ESI) m/z: 433 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 2.12 (s, 3H), 3.35 (s, 2H), 4.21 (d, J=8.0 Hz, 1H), 4.64 (d, J=8.0 Hz, 1H), 6.81-6.85 (m, 3H), 6.99-7.01 (m, 2H), 7.13-7.19 (m, 5H); 19F-NMR (400 MHz, CD3OD) δ (ppm): −105.66 (s), −118.17 (s).

Workup

  1. customMethanol was removed under reduced pressure
  2. customThe crude was purified by prep-HPLC

Sources & evidence

ORD record
ord-1368e7f85af04b149269e69b51eef37a
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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