Acetic Acid → 8-(4-((dimethylamino)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 907882Notes

Reaction equation

HRID 907882 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]3=[N:14][NH:15][C:16](=[O:21])[C:17]4[CH:18]=[CH:19][CH:20]=[C:11]([C:12]=43)[NH:10][CH:9]2[C:22]2[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=2)=[CH:4][CH:3]=1.[CH3:30][NH:31][CH3:32].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:30][N:31]([CH2:26][C:25]1[CH:28]=[CH:29][C:22]([CH:9]2[NH:10][C:11]3[C:12]4[C:13](=[N:14][NH:15][C:16](=[O:21])[C:17]=4[CH:18]=[CH:19][CH:20]=3)[CH:8]2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:23][CH:24]=1)[CH3:32]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 136344749HCID 136344749, compound

Product 1

HCID 1360568808-(4-((dimethylamino)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 24.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 4-(9-(4-fluorophenyl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (80 mg, 0.21 mmol), dimethylamine (47 mg, 1.04 mmol) and acetic acid (62 mg, 1.04 mmol) in methanol (50 mL) was stirred at room temperature for 60 min. Then the mixture was cooled to 0° C. Sodium cyanoborohydride (20 mg, 0.3 mmol) was added. After the addition, the mixture was stirred at room temperature for overnight. Methanol was removed under reduced pressure. The crude product was purified by pre-HPLC to give 8-(4-((dimethylamino)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (21 mg, yield 24%). 1H-NMR (400 MHz, CD3OD) δ (ppm): 2.82 (s, 6H), 4.26 (s, 2H), 4.32 (d, J=8.0 Hz, 1H), 4.77 (d, J=8.0 Hz, 1H), 6.93-6.95 (m, 2H), 7.10-7.11 (m, 2H), 7.23 (m, 1H), 7.40-7.41 (m, 4H), 7.59 (d, J=8.0 Hz, 1H), 7.65 (t, J=8.0 Hz, 1H). 19F-NMR (400 MHz, CD3OD) δ (ppm): −77.09, −118.00; LC-MS (ESI) m/z: 415 (M+1)+.

Workup

  1. temperatureThen the mixture was cooled to 0° C
  2. additionAfter the addition
  3. stirringthe mixture was stirred at room temperature for overnight
  4. customMethanol was removed under reduced pressure
  5. customThe crude product was purified by pre-HPLC

Sources & evidence

ORD record
ord-368014d52b9e4816a33383a14e6b4057
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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