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

HRID 908006Notes

Reaction equation

HRID 908006 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.C(Cl)Cl.[CH2:33]([NH:35][CH2:36][CH3:37])[CH3:34].[BH4-].[Na+]>C(O)(=O)C>[CH2:33]([N:35]([CH2:26][C:25]1[CH:24]=[CH:23][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:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:29][CH:28]=1)[CH2:36][CH3:37])[CH3:34]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8021DiethylamineHCID 4311764Sodium borohydrideHCID 136344749HCID 136344749, compound

Product 1

HCID 1363851998-(4-((Diethylamino)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 9.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 4-(9-(4-fluorophenyl)-3-oxo-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (260 mg, 0.68 mmol) in dryness DCM (15 mL) was added acetic acid (0.2 mL) followed by diethylamine (148 mg, 2.03 mmol). After the addition, the mixture was stirred at room temperature overnight. Then sodium borohydride (212 mg, 1.01 mmol) was added to the mixture at 0° C. The mixture was stirred at this temperature for 12 hr. DCM was removed under reduced pressure. The residue was washed with ethyl acetate/methanol (10/1) and filtered. The filtrate was concentrated to give the crude product, which was purified by flash chromatography to give the title compound as white solid (27.3 mg, yield 9%). LC-MS (ESI) m/z: 442 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 3.12-3.17 (m, 4H), 4.27 (s, 2H), 4.34 (d, 1H), 4.78 (d, 1H), 6.91 (t, 2H), 7.09-7.12 (m, 1H), 7.38-7.45 (m, 4H), 7.56-7.58 (m, 1H), 7.64 (t, 1H).

Workup

  1. additionAfter the addition
  2. stirringThe mixture was stirred at this temperature for 12 hr
  3. customDCM was removed under reduced pressure
  4. washThe residue was washed with ethyl acetate/methanol (10/1)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customto give the crude product, which
  8. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-59523ba851cb4d2a90eb052b415a70c8
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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