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Binap, (A+-)- → 8-Fluoro-1-{[(7R,8R)-7-methyl-1,4-dioxaspiro[4.5]dec-8-yl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile

HRID 1971015
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HRID 1971015 반응식
Cl[C:2]1[C:14]2[C:13]3[CH:12]=[C:11]([F:15])[CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:16]#[N:17])=[CH:4][N:3]=1.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+].[CH3:70][C@H:71]1[C@H:80]([NH2:81])[CH2:79][CH2:78][C:73]2([O:77][CH2:76][CH2:75][O:74]2)[CH2:72]1>CCOC(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].COCCOC>[F:15][C:11]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[C:5]([C:16]#[N:17])=[CH:4][N:3]=[C:2]([NH:81][C@@H:80]4[CH2:79][CH2:78][C:73]5([O:74][CH2:75][CH2:76][O:77]5)[CH2:72][C@H:71]4[CH3:70])[C:14]=3[C:13]=2[CH:12]=1
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참가 물질

8

반응물 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 591984921-chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrileHCID 59543149(7R,8R)-7-Methyl-1,4-dioxaspiro[4.5]decan-8-amine

생성물 1

HCID 686699758-Fluoro-1-{[(7R,8R)-7-methyl-1,4-dioxaspiro[4.5]dec-8-yl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

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온도
85 °C

실험 절차

A flask containing 1-chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile (1.50 g, 6.11 mmol), BINAP (570 mg, 0.916 mmol), Pd2(dba)3 (280 mg, 0.305 mmol), and NaOtBu (1.88 g, 19.5 mmol) was evacuated and refilled with nitrogen (×3). Degassed DME (50 mL) and (7R,8R)-7-methyl-1,4-dioxaspiro[4.5]decan-8-amine (1.26 g, 7.33 mmol) were added to the mixture. The reaction mixture was heated to 85° C. overnight, cooled to room temperature, diluted with EtOAc, and washed with water and brine. The organic layer was dried (sodium sulfate), concentrated, and purified by flash chromatography to afford the title compound. LRMS (APCI) calc'd for (C21H21FN4O2) [M+H]+, 381.2. found 381.1.

후처리

  1. customwas evacuated
  2. additionrefilled with nitrogen (×3)
  3. temperaturecooled to room temperature
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried (sodium sulfate)
  6. concentrationconcentrated
  7. custompurified by flash chromatography

출처 및 근거

ORD 기록
ord-3b4a170ea30b48e780bdf4f249cea4c7
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08431569B2

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