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

HRID 1971019ノート

反応式

HRID 1971019 の反応式
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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0dfb8b7953dc4fbc93bc65416f2c4975
出典データセット
uspto-grants-2013_04
特許番号
US08431569B2

反応ノート

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