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Dichloromethane → 8-(4-((4-Ethyl-3-methylpiperazin-1-yl)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 1968054
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HRID 1968054 반응식
[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[NH:12][CH:13]([C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=4)[CH:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:5]([C:6]=23)=[N:4][NH:3]1.C(Cl)Cl.[CH2:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH:35]1[CH3:40])[CH3:33].[BH4-].[Na+]>CC(O)=O>[CH2:32]([N:34]1[CH2:39][CH2:38][N:37]([CH2:25][C:24]2[CH:23]=[CH:22][C:21]([CH:13]3[NH:12][C:7]4[C:6]5[C:5](=[N:4][NH:3][C:2](=[O:1])[C:11]=5[CH:10]=[CH:9][CH:8]=4)[CH:14]3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:28][CH:27]=2)[CH2:36][CH:35]1[CH3:40])[CH3:33]
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참가 물질

6

반응물 4

HCID 6344DichloromethaneHCID 4311764Sodium borohydrideHCID 177503651-Ethyl-2-methylpiperazineHCID 1363447524-(3-Oxo-9-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde

생성물 1

HCID 1363685498-(4-((4-Ethyl-3-methylpiperazin-1-yl)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one수율 81.6%

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

To a stirred solution of 4-(3-oxo-9-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (86 mg, 0.23 mmol) in dryness DCM (15 mL) was added HOAc followed by 1-ethyl-2-methylpiperazine (90 mg, 0.7 mmol), after the addition the mixture was stirred at room temperature overnight. Then the mixture was cooled to 0° C. Sodium borohydride (85 mg, 1.4 mmol) was added. After the addition, 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 prep-HPLC to give the title compound as white solid (90 mg, yield 71%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 1.30 (t, 3H), 1.42 (m, 3H), 3.23 (s, 1H), 3.47-3.56 (m, 6H), 3.80 (t, 2H), 4.46 (m, 3H) 4.91 (m, 10H), 7.20-7.29 (m, 3H), 7.30-7.32 (m, 3H), 7.46-7.48 (m, 3H), 7.59 (m, 1H), 7.69 (t, 1H). LC-MS (ESI) m/z: 552 (M+1)+.

후처리

  1. additionafter the addition the mixture
  2. temperatureThen the mixture was cooled to 0° C
  3. additionAfter the addition
  4. stirringthe mixture was stirred at this temperature for 12 hr
  5. customDCM 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, which
  10. customwas purified by prep-HPLC

출처 및 근거

ORD 기록
ord-6ad3efc5949e44b9bf85ada267347fdb
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08420650B2

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