Diisopropylethylamine → 4-amino-N-(2,2-dimethyl-3-pyrrolidin-1-yl-propyl)-3-methoxy-benzamide

HRID 2234473Notes

Reaction equation

HRID 2234473 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][CH3:12].[CH3:13][C:14]([CH3:23])([CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[CH2:15][NH2:16].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:16][CH2:15][C:14]([CH3:23])([CH3:13])[CH2:17][N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:8])=[CH:4][C:3]=1[O:11][CH3:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2880572486-69-3HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45088486beta,beta-Dimethyl-1-pyrrolidinepropanamine

Product 1

HCID 686858814-amino-N-(2,2-dimethyl-3-pyrrolidin-1-yl-propyl)-3-methoxy-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the 4-amino-3-methoxy-benzoic acid (Aldrich; 2 g, 12 mmol) and 2,2-dimethyl-3-pyrrolidin-1-yl-propan-1-amine (WO 2004033419; 2.1 g, 13.2 mmol) were dissolved in DMF (50 mL), and to the solution was added DIPEA (3.1 g, 4.2 mL). The reaction was cooled with an ice-bath, and to it was added, portionwise, HATU (5.02 g, 13.2 mmol). The reaction mixture was stirred at ambient temperature for 18 hours. The solvent was evaporated, and the residue was partitioned between Ethyl Acetate (100 mL), and saturated aqueous sodium carbonate solution (3×40 mL), washed with brine (3×40 mL), dried over anhydrous Magnesium sulphate, filtered, and the solvent evaporated. The residue was purified by chromatography on a silica column pre-conditioned with Ethyl acetate and eluted with 10% MeOH-DCM+1% NH3. Those fractions containing the desired product were combined and the solvent was evaporated to yield the title compound as a pale brown gum, which crystallised on standing. (500 mgs; 14%).

Workup

  1. temperatureThe reaction was cooled with an ice-bath
  2. additionto it was added
  3. customThe solvent was evaporated
  4. customthe residue was partitioned between Ethyl Acetate (100 mL), and saturated aqueous sodium carbonate solution (3×40 mL)
  5. washwashed with brine (3×40 mL)
  6. dry with materialdried over anhydrous Magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. customThe residue was purified by chromatography on a silica column pre-conditioned with Ethyl acetate
  10. washeluted with 10% MeOH-DCM+1% NH3
  11. additionThose fractions containing the desired product
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-84021aabb5324d7592f34bf22b9f6cfa
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

Loading…