Toluene → HCID 68185438, compound

HRID 2366967Notes

Reaction equation

HRID 2366967 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[CH:33][C:34]([NH2:37])=[N:35][CH:36]=2)O1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:31]3[CH:36]=[N:35][C:34]([NH2:37])=[CH:33][CH:32]=3)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 68185438HCID 68185438, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

1-Methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (1 g, 2.71 mmol) (for a preparation see Example 4) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinamine (0.487 g, 2.213 mmol) were combined in ethanol (4.7 ml) and toluene (4.70 ml) to give a light yellow solution. K2CO3 (0.449 g, 3.25 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (0.156 g, 0.135 mmol) were added and the resulted mixture was stirred at 90° C. under nitrogen for 16 h then was cooled to room temperature and concentrated in vacuo. The residue was partitioned between water (40 mL) and EtOAc (50 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (50 mL) and the combined organic phases were washed with brine (100 mL), dried over Na2SO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 12 to 63% AcOEt in Hexanes followed by 10% (2M NH3 in MeOH) in DCM) gave a residue which was further purified by flash chromatography on silica gel (gradient: 1 to 5% (2M NH3 in MeOH) in DCM) to give 1-methylethyl[(2S,4R)-1-acetyl-6-(6-amino-3-pyridinyl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (0.74 g, 1.885 mmol, 69.6% yield) as a yellow foam.

Workup

  1. additionwere added
  2. temperaturethen was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water (40 mL) and EtOAc (50 mL)
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (50 mL)
  7. washthe combined organic phases were washed with brine (100 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue by flash chromatography on silica gel (gradient: 12 to 63% AcOEt in Hexanes followed by 10% (2M NH3 in MeOH) in DCM)
  11. customgave a residue which
  12. customwas further purified by flash chromatography on silica gel (gradient: 1 to 5% (2M NH3 in MeOH) in DCM)

Sources & evidence

ORD record
ord-4242f53c0c4445059e71398589577f53
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…