Acetic Acid → 8-(4-((dimethylamino)methyl)phenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 1467585Notes

Reaction equation

HRID 1467585 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[CH:7]1[C:12]2=[N:13][NH:14][C:15](=[O:20])[C:16]3[CH:17]=[CH:18][CH:19]=[C:10]([C:11]=32)[NH:9][CH:8]1[C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1.[C:29](O)(=O)C.[BH3-][C:34]#[N:35].[Na+]>C(#N)C>[CH3:29][N:35]([CH2:25][C:24]1[CH:27]=[CH:28][C:21]([CH:8]2[NH:9][C:10]3[C:11]4[C:12](=[N:13][NH:14][C:15](=[O:20])[C:16]=4[CH:17]=[CH:18][CH:19]=3)[CH:7]2[C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)=[CH:22][CH:23]=1)[CH3:34]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 1363685674-(9-(1-methyl-1H-imidazol-2-yl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde

Product 1

HCID 1360568778-(4-((dimethylamino)methyl)phenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 34%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(9-(1-methyl-1H-imidazol-2-yl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (80 mg, 0.22 mmol), acetic acid (60 uL) and 27% dimethylamine alcohol solution (2.5 mL, 15 mmol) in acetonitrile (7 mL) was stirred at room temperature for 4 h. Then the mixture was cooled to 0° C. NaBH3CN (36 mg, 0.67 mmol) was added. After the addition, the mixture was stirred at room temperature for 4 hr. Methanol was removed under reduced pressure. The residue was washed with ethyl acetate and filtered. The filtrate was concentrated to give 8-(4-((dimethylamino)methyl)phenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (30 mg, yield 34%) as a white solid. 1H-NMR: (400 MHz, DMSO-d6) δ (ppm): 2.11 (s, 6H), 3.36 (s, 2H), 3.37 (s, 3H), 4.65 (d, J=10.4 Hz, 1H), 4.92 (d, J=10.4 Hz, 1H), 6.76 (s, 1H), 6.89 (s, 1H), 7.20 (d, J=7.6 Hz, 3H), 7.35 (d, J=8.0 Hz, 2H), 7.43 (d, J=6.8 Hz, 1H), 7.62 (t, J=7.8 Hz, 1H); LC-MS (ESI) m/z: 401 (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 4 hr
  4. customMethanol was removed under reduced pressure
  5. washThe residue was washed with ethyl acetate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-7aec010b37164c55ae5d325e4949803a
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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