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

HRID 1971019Notes

Reaction equation

HRID 1971019 reaction equation
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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0dfb8b7953dc4fbc93bc65416f2c4975
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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