Hydrazine hydrate (1:1) → 9-(3-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 1467572Notes

Reaction equation

HRID 1467572 reaction equation
[C:1]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:15]=[C:16]([CH:20]3[C:29](=O)[C:28]4[C:27]([C:31]([O:33]C)=O)=[CH:26][CH:25]=[CH:24][C:23]=4[NH:22][CH:21]3[C:35]3[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=3)[CH:17]=[CH:18][CH:19]=2)=[O:13])[CH2:8][CH2:7]1)(=[O:5])[CH:2]([CH3:4])[CH3:3].O.[NH2:42][NH2:43]>CO>[C:1]([N:6]1[CH2:7][CH2:8][N:9]([C:12]([C:14]2[CH:15]=[C:16]([CH:20]3[C:29]4=[N:42][NH:43][C:31](=[O:33])[C:27]5[CH:26]=[CH:25][CH:24]=[C:23]([C:28]=54)[NH:22][CH:21]3[C:35]3[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=3)[CH:17]=[CH:18][CH:19]=2)=[O:13])[CH2:10][CH2:11]1)(=[O:5])[CH:2]([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67259841Methyl 3-(3-(4-isobutyryl piperazine-1-carbonyl)phenyl)-4-oxo-2-(pyridin-4-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate

Product 1

HCID 1363852619-(3-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of methyl 3-(3-(4-isobutyryl piperazine-1-carbonyl)phenyl)-4-oxo-2-(pyridin-4-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate (140 mg, 0.26 mmol) in 85% hydrazine monohydrate (10 mL) and methanol (3 mL) was stirred at 25° C. for 4 hr. The mixture was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by prep-HPLC to give compound 9-(3-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (11 mg, yield 8%) as a white solid. 1H-NMR (400 MHz, CD3OD) δ (ppm): 1.11-1.13 (m, 6H), 2.95-2.98 (m, 1 H), 3.26-3.68 (m, 8H), 4.40-4.42 (d, J=8.4 Hz, 1H), 4.82-4.84 (d, J=8.4 Hz, 1H), 7.19-7.32 (m, 4H), 7.36-7.39 (m, 3H), 7.59-7.68 (m, 2H), 8.41-8.42 (d, J=6.0 Hz, 2H); LC-MS (ESI) m/z: 523 (M+1)+.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (50 mL×3)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto give crude product
  6. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-a712c9c64b3645e0ade6aa58159f5698
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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