Trifluoroacetic acid → 8,9-Bis(4-fluorophenyl)-8,9-dihydro-2h-pyrido[4,3,2-de]phthalazin-3(7h)-one

HRID 1967999Notes

Reaction equation

HRID 1967999 reaction equation
COC(OC)C1C=CC(C2C([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)C(=O)C3C(C(OC)=O)=CC=CC=3N2)=CC=1.CO[CH:36]([O:66]C)[C:37]1[CH:42]=[CH:41][C:40]([CH:43]2[CH:52]([C:53]3[CH:58]=[CH:57][C:56]([F:59])=[CH:55][CH:54]=3)[C:51](=O)[C:50]3[C:49]([C:61]([O:63]CC)=O)=[CH:48][CH:47]=[CH:46][C:45]=3[NH:44]2)=[CH:39][CH:38]=1.FC1C=CC([CH:75]2[CH:84](C3C=CC(F)=CC=3)[C:83](=O)[C:82]3[C:81]([C:93](OC)=[O:94])=[CH:80][CH:79]=[CH:78][C:77]=3[NH:76]2)=CC=1.O.[NH2:98][NH2:99].FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[F:59][C:56]1[CH:57]=[CH:58][C:53]([CH:52]2[C:51]3=[N:98][NH:99][C:61](=[O:63])[C:49]4[CH:48]=[CH:47][CH:46]=[C:45]([C:50]=43)[NH:44][CH:43]2[C:40]2[CH:41]=[CH:42][C:37]([CH:36]=[O:66])=[CH:38][CH:39]=2)=[CH:54][CH:55]=1.[F:59][C:56]1[CH:57]=[CH:58][C:53]([CH:75]2[NH:76][C:77]3[C:82]4[C:83](=[N:98][NH:99][C:93](=[O:94])[C:81]=4[CH:80]=[CH:79][CH:78]=3)[CH:84]2[C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)=[CH:54][CH:55]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 24654Hydrazine hydrate (1:1)HCID 67259957Methyl 2-(4-(dimethoxymethyl)phenyl)-3-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateHCID 67260025Ethyl 2-(4-(dimethoxymethyl)phenyl)-3-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateHCID 67260993Methyl 2,3-bis-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

Product 2

HCID 1361401178,9-Bis(4-fluorophenyl)-8,9-dihydro-2h-pyrido[4,3,2-de]phthalazin-3(7h)-oneHCID 136344749HCID 136344749, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of methyl 2-(4-(dimethoxymethyl)phenyl)-3-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate, ethyl 2-(4-(dimethoxymethyl)phenyl)-3-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate and methyl 2,3-bis-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (440 mg) and hydrazine monohydrate (20 mL) was stirred under room temperature for overnight. The resulting mixture was evaporated under reduced pressure to 10 mL and then filtered, 400 mg of the crude products were obtained. To a solution of this crude products (400 mg) in dichloromethane was added trifluoroacetic acid (1 ml) at 0° C. The mixture was stirred at room temperature for 1 hr. Then the mixture was neutralized with potassium carbonate. 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 the crude. The crude product was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 10:1 to 1:1) to give 4-(9-(4-fluorophenyl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (80 mg) and 8,9-bis(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (36 mg). 4-(9-(4-fluorophenyl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde: LC-MS (ESI) m/z: 368 (M+1)+. 8,9-bis(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one: 1H-NMR (400 MHz, CD3OD) δ (ppm): 4.29 (d, J=8.0 Hz, 1H), 4.70 (d, J=8.0 Hz, 1H), 6.92-7.00 (m, 4H), 7.08-7.10 (m, 2H), 7.20-7.20 (m, 1H), 7.28-7.32 (m, 2H), 7.59 (m, 1H), 7.63-7.67 (m, 1H). 19F-NMR (400 MHz, CD3OD) δ (ppm): −116.77, −118.23; LC-MS (ESI) m/z: 376 (M+1)+. solid.

Workup

  1. customThe resulting mixture was evaporated under reduced pressure to 10 mL
  2. filtrationfiltered
  3. custom400 mg of the crude products were obtained
  4. stirringThe mixture was stirred at room temperature for 1 hr
  5. extractionThe mixture was extracted with ethyl acetate (50 mL×3)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customto give the crude
  10. customThe crude product was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 10:1 to 1:1)

Sources & evidence

ORD record
ord-f7f453f4e1e44fd4b54c7502fee2b2e7
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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