Dichloromethane → HCID 136056853, compound

HRID 1967990Notes

Reaction equation

HRID 1967990 reaction equation
[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[NH:12][CH:13]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:14]([C:15]4[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=4)[CH:18]=O)[C:5]([C:6]=23)=[N:4][NH:3]1.ClCCl.[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.[BH4-].[Na+]>C(O)(=O)C>[CH3:32][N:33]1[CH2:38][CH2:37][N:36]([CH2:18][C:17]2[CH:16]=[C:15]([CH:14]3[C:5]4=[N:4][NH:3][C:2](=[O:1])[C:11]5[CH:10]=[CH:9][CH:8]=[C:7]([C:6]=54)[NH:12][CH:13]3[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:22]=[CH:21][CH:20]=2)[CH2:35][CH2:34]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 531671-MethylpiperazineHCID 4311764Sodium borohydrideHCID 136344723HCID 136344723, compound

Product 1

HCID 136056853HCID 136056853, compoundYield 12.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 3-(3-oxo-8-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-9-yl)benzaldehyde (150 mg, 0.4 mmol) in dryness dichloromethane (10 mL) was added acetic acid followed by 1-methylpiperazine (121 mg, 1.2 mmol). After the addition, the mixture was stirred at room temperature for 1 h, Then the mixture was cooled to 0° C. Sodium borohydride (130 mg, 0.2 mmol) was added. After the addition, the mixture was stirred at this temperature for 3 hr. Dichloromethane 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. The crude product was purified by pre-HPLC to give 9-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one as white solid (22 mg, yield 12%). 1H-NMR (400 MHz, CD3OD) δ (ppm): 2.31 (s, 3H), 2.36-2.48 (m, 8H), 3.37-3.48 (dd, 2H), 4.30 (dd, 1H), 4.71 (dd, 1H), 7.01 (s, 1H), 7.05 (dd, 1H), 7.17-7.23 (m, 5H), 7.25-7.28 (m, 2H), 7.56 (dd, 1H), 7.61-7.65 (t, 1H); LC-MS (ESI) m/z: 452 (M+1)+.

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was cooled to 0° C
  3. additionAfter the addition
  4. stirringthe mixture was stirred at this temperature for 3 hr
  5. customDichloromethane was removed under reduced pressure
  6. washThe residue was washed with ethyl acetate/methanol (10/1)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customto give the crude product
  10. customThe crude product was purified by pre-HPLC

Sources & evidence

ORD record
ord-0d355bc69be0490eb3e8ee769cf2c1ca
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

Loading…