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

HRID 1467745Notes

Reaction equation

HRID 1467745 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-084fc91963ef4d9e8b64b3b8c5c2a049
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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