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

HRID 1967932Notes

Reaction equation

HRID 1967932 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:19]=[CH:18][C:17]([CH:20]4[C:29](=O)[C:28]5[C:27]([C:31](OC)=[O:32])=[CH:26][CH:25]=[CH:24][C:23]=5[NH:22][CH:21]4[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:16][CH:15]=3)=[O:13])[CH2:8][CH2:7]2)=O)[CH2:3][CH2:2]1.[OH2:41].[NH2:42][NH2:43]>CO>[CH:1]1([C:4]([N:6]2[CH2:7][CH2:8][N:9]([C:12]([C:14]3[CH:15]=[CH:16][C:17]([CH:20]4[C:29]5=[N:42][NH:43][C:31](=[O:32])[C:27]6[CH:26]=[CH:25][CH:24]=[C:23]([C:28]=65)[NH:22][CH:21]4[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)=[CH:18][CH:19]=3)=[O:13])[CH2:10][CH2:11]2)=[O:41])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67258433Methyl 3-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate

Product 1

HCID 1363853009-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 22%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of methyl 3-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (90 mg, 0.16 mmol) in 85% hydrazine monohydrate (5 mL) and methanol (2 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 9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (18 mg, yield 22%) as a white solid. 1H-NMR (400 MHz, CD3OD) δ (ppm): 0.86-0.94 (m, 4H), 2.00 (s, 1H), 3.33-3.82 (m, 8H), 4.41-4.43 (d, J=8.4 Hz, 1H), 4.78-4.80 (d, J=8.4 Hz, 1H), 7.21-7.27 (m, 6H), 7.30-7.35 (m, 4H), 7.58-7.60 (m, 1H), 7.65-7.69 (t, J=8.0 Hz, 4H); LC-MS (ESI) m/z: 520 (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-9c5e9d87374c4cfea47bd8c14a6c2b45
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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