N-Methylaniline → 3,3-Dimethyl-6-(methyl-phenyl-amino)-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 1475357Notes

Reaction equation

HRID 1475357 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14](Cl)[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.ClC1C(P(C2CCCCC2)C2CCCCC2)=C(C2C(OC(C)C)=CC=CC=2OC(C)C)C=CC=1.COC(C)(C)C.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14]([N:21]([CH3:20])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 6

HCID 7515N-MethylanilineHCID 15413tert-Butyl methyl etherHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 86723969tert-Butyl 6-chloro-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylateHCID 118310965HCID 118310965, compound

Product 1

HCID 867239723,3-Dimethyl-6-(methyl-phenyl-amino)-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl esterYield 77.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 6-chloro-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (116 mg, 0.41 mmol), N-methylaniline (89 μL, 0.82 mmol), RuPhos (20 mg, 0.041 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-iso-propoxy-1,-1′-biphenyl)[2-(2-aminoethylphenyl)palladium(II), methyl-tert-butylether adduct (33 mg, 0.041 mmol) and NaOtBu (99 mg, 1.8 mmol) in toluene (2 mL) was evacuated and flushed with nitrogen. The mixture was stirred at 110° C. for 5 h. The mixtures was allowed to cool and then partitioned between EtOAc and water. The organic extract was washed with brine, dried (Na2SO4) and evaporated in vacuo. Chromatography (SiO2; gradient elution with 5-20% EtOAc in petrol) gave the title compound (112 mg, 56%) as a colourless solid. MS: [M+H]+=354.

Workup

  1. customflushed with nitrogen
  2. temperatureto cool
  3. custompartitioned between EtOAc and water
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. washChromatography (SiO2; gradient elution with 5-20% EtOAc in petrol)

Sources & evidence

ORD record
ord-f45344a620944540b10f78f7aef4d46a
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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