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Binap, (A+-)- → 1,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 2061472
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HRID 2061472 반응식
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:12].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>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].O1CCOCC1>[Cl:8][C:6]1[CH:5]=[C:4]([F:9])[C:3]2[NH:10][C:11](=[O:12])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:2]=2[CH:7]=1
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참가 물질

5

반응물 2

HCID 634876Binap, (A+-)-HCID 596832771,1-Dimethylethyl 4-({[(2-bromo-4-chloro-6-fluorophenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

생성물 1

HCID 596832761,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매
HCID 31275
1,4-Dioxane
용매

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온도
80 °C

실험 절차

Under an argon atmosphere, 1,1-dimethylethyl 4-({[(2-bromo-4-chloro-6fluorophenyl)amino]carbonyl}amino)-1-piperidinecarboxylate (D7) (1.09 mmol, 0.493 g), 1,4-dioxane (4.4 ml), Pd2 dba3 (0.05 eq., 0.054 mmol, 50 mg), BINAP (0.055 eq., 0.059 mmol, 37 mg), NatBuO (1.5 eq., 1.63 mmol, 157 mg) were mixed together and heated to 80° C. under argon for 4 days. The reaction mixture was cooled to room temperature, quenched with water and the aqueous solution obtained was extracted with ethyl acetate. The solvent was evaporated and the crude was purified by MDAP. Fractions were collected and the solvent evaporated to yield the title compound, 15 mg, 3%, M+−H=368.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water
  3. customthe aqueous solution obtained
  4. extractionwas extracted with ethyl acetate
  5. customThe solvent was evaporated
  6. customthe crude was purified by MDAP
  7. customFractions were collected
  8. customthe solvent evaporated

출처 및 근거

ORD 기록
ord-01cd19f9c8c44a73a63aea8453ad8e83
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08283364B2

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