Binap, (A+-)- → 1-[(4-{[tert-Butyl(dimethyl)silyl]oxy}-3-fluorocyclohexyl)amino]-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile

HRID 1971019노트

반응식

HRID 1971019 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.[K+].[Si:70]([O:77][CH:78]1[CH2:83][CH2:82][CH:81]([NH2:84])[CH2:80][CH:79]1[F:85])([C:73]([CH3:76])([CH3:75])[CH3:74])([CH3:72])[CH3:71]>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>[Si:70]([O:77][CH:78]1[CH2:83][CH2:82][CH:81]([NH:84][C:2]2[C:14]3[C:13]4[CH:12]=[C:11]([F:15])[CH:10]=[CH:9][C:8]=4[NH:7][C:6]=3[C:5]([C:16]#[N:17])=[CH:4][N:3]=2)[CH2:80][CH:79]1[F:85])([C:73]([CH3:76])([CH3:75])[CH3:74])([CH3:72])[CH3:71]

참가 물질

8

반응물 4

HCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 591984921-chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrileHCID 595431224-{[tert-Butyl(dimethyl)silyl]oxy}-3-fluorocyclohexanamine

생성물 1

HCID 595431201-[(4-{[tert-Butyl(dimethyl)silyl]oxy}-3-fluorocyclohexyl)amino]-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile

시약·촉매·용매 3

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

반응 조건

온도
85 °C

실험 절차

A flask containing 1-chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile (Example 38 Step 4, 250 mg, 1.02 mmol), BINAP (95 mg, 0.15 mmol), Pd2(dba)3 (47 mg, 0.051 mmol), and KOtBu (365 mg, 3.26 mmol) was evacuated and refilled with nitrogen (×3). Degassed DME (5 mL) and 4-{[tert-butyl(dimethyl)silyl]oxy}-3-fluorocyclohexanamine (327 mg, 1.32 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 (C24H30F2N4OSi) [M+H]+, 457.2. found 457.1.

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-0dfb8b7953dc4fbc93bc65416f2c4975
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431569B2

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