Binap, (A+-)- → 4-(2-[(4-Chloro-1-oxo-1,2-dihydro-phthalazin-6-ylamino)-methyl]-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1803622노트

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HRID 1803622 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[Cl:13].BrC1C=C2C(C(Cl)=NNC2=O)=CC=1.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=2[CH2:48][NH2:49])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>CC(N(C)C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=2[CH2:48][NH:49][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8](=[O:12])[NH:7][N:6]=[C:5]3[Cl:13])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

참가 물질

8

반응물 5

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-oneHCID 674169997-bromo-4-chloro-2H-phthalazin-1-oneHCID 674174384-(2-Aminomethyl-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 674170634-(2-[(4-Chloro-1-oxo-1,2-dihydro-phthalazin-6-ylamino)-methyl]-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester수율 18%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 31374Dimethylacetamide용매

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온도
90 °C

실험 절차

A mixture of 6-bromo-4-chloro-2H-phthalazin-1-one and 7-bromo-4-chloro-2H-phthalazin-1-one (300 mg, 1.16 mmol), 4-(2-aminomethyl-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (338 mg, 1.05 mmol), Pd2(dba)3 (110 mg, 0.12 mmol), BINAP (217 mg, 0.35 mmol) and NaOt-Bu (327 mg, 3.48 mmol) in DMA (10 mL) was purged with nitrogen for 10 min. The mixture was heated at 90° C. for 1.5 h. The mixture was allowed to cool and diluted with ethyl acetate (30 mL) and washed with ammonium chloride (25 mL). The organic layer was dried and concentrated. Chromatography on silica yielded the title compound (102 mg, 18%) m/z (M+H)=500.32.

후처리

  1. customwas purged with nitrogen for 10 min
  2. temperatureto cool
  3. additiondiluted with ethyl acetate (30 mL)
  4. washwashed with ammonium chloride (25 mL)
  5. customThe organic layer was dried
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-c0c80cf9237148469325d6943bf0c05a
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08349836B2

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