HCID 12343620, compound → HCID 11282350, compound

HRID 131519Notes

Reaction equation

HRID 131519 reaction equation
[CH3:1][C:2]([CH3:22])([CH3:21])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([NH:13][CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[C:10]([CH3:12])[CH:11]=1)=[O:4].C([Li])CCC.[CH2:28]([O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38](OC)=O)=[CH:33][CH:32]=1)[CH3:29]>C1COCC1>[CH2:28]([O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38]2[N:13]([CH2:14][CH:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)[C:9]3=[N:8][CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:22])([CH3:21])[CH3:1])[CH:11]=[C:10]3[CH:12]=2)=[CH:33][CH:32]=1)[CH3:29]

Participants

5

Reactant 3

HCID 12343620HCID 12343620, compoundHCID 59732490HCID 59732490, compoundHCID 178418339Butyllithium

Product 1

HCID 11282350HCID 11282350, compoundYield 25.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of 2,2-dimethyl-N-[5-methyl-6-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]-3-pyridinyl]-propanamide (2.0 g, 6.55 mmol) in THF (70 ml) at −78° C. was added n-butyl lithium (11.5 ml of 2.0 M solution in cyclohexane, 23.0 mmol). The mixture was stirred for one hour at −20° C. and then cooled to −78° C. To this reaction mixture was cannulated a solution of methyl 4-ethoxy-benzeneacetate (1.72 g, 7.88 mmol) in THF (50 ml) at −78° C. After stirring for 3 hours at room temperature, the mixture was quenched with NaHCO3 saturated aqueous solution (200 ml) and diluted with EtOAc (100 ml). The phases were separated and the aqueous phase was back-extracted with additional EtOAc (100 ml). The organic phases were combined, dried with MgSO4, filtered and concentrated in vacuo. The residue was purified using silica gel flash chromatography ([3% MeOH+0.5% NH4OHaq] in CH2Cl2) to provide 750 mg of the title compound N-[2-[(4-ethoxyphenyl)methyl]-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-2,2-dimethyl-propanamide. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.31 (m, 2 H) 1.34 (s, 9 H) 1.40 (t, J=7.03 Hz, 3 H) 1.56 (m, 2 H) 2.04 (m, 1 H) 3.22 (m, 2 H) 3.35 (m, 2 H) 3.90 (t, J=3.32 Hz, 2 H) 4.00 (m, 2 H) 4.06 (s, 2 H) 6.12 (s, 1 H) 6.83 (m, 2 H) 7.07 (d, J=8.79 Hz, 2 H) 7.32 (m, 1 H) 8.09 (d, J=2.34 Hz, 1 H) 8.15 (d, J=2.34 Hz, 1 H). MS (ESI) (M+H)+: 451.

Workup

  1. temperaturecooled to −78° C
  2. customat −78° C
  3. stirringAfter stirring for 3 hours at room temperature
  4. customthe mixture was quenched with NaHCO3 saturated aqueous solution (200 ml)
  5. additiondiluted with EtOAc (100 ml)
  6. customThe phases were separated
  7. extractionthe aqueous phase was back-extracted with additional EtOAc (100 ml)
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified

Sources & evidence

ORD record
ord-8fbbcd331ffc454389b2179ceff35059
Source dataset
uspto-grants-2008_06
Patent number
US07384955B2

Reaction notes

Loading…