Diisopropylethylamine → N-{5-[Acetyl(methyl)amino]-2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-2,2-difluoropropanamide

HRID 1987214Notes

Reaction equation

HRID 1987214 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]1[CH:27]=[C:28]([N:40]([CH3:44])[C:41](=[O:43])[CH3:42])[CH:29]=[CH:30][C:31]=1[NH:32][CH2:33][CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.[F:45][C:46]([F:51])([CH3:50])[C:47](O)=[O:48].CCN(C(C)C)C(C)C>CN(C=O)C>[C:41]([N:40]([CH3:44])[C:28]1[CH:29]=[CH:30][C:31]([NH:32][CH2:33][CH:34]2[CH2:35][CH2:36][O:37][CH2:38][CH2:39]2)=[C:26]([NH:25][C:47](=[O:48])[C:46]([F:51])([F:45])[CH3:50])[CH:27]=1)(=[O:43])[CH3:42]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27828252,2-Difluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57441082N-{3-Amino-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-N-methylacetamide

Product 1

HCID 57441090N-{5-[Acetyl(methyl)amino]-2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-2,2-difluoropropanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (1.44 g, 3.78 mmol) and N-{3-amino-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-N-methylacetamide (1.00 g, 3.60 mmol) (for preparation, see Example 1, steps B to E) were added to a solution of 2,2-difluoropropanoic acid (0.40 g, 3.60 mmol) and DIPEA (0.75 mL, 4.32 mmol) in DMF (100 mL) at room temperature. The reaction mixture was stirred overnight. The solvent was concentrated and the crude product was recovered in EtOAc. The organic was washed with water, saturated NaHCO3 solution and brine. The organic layer was dried over anhydrous Na2SO4 and filtered. The solvent was concentrated giving the title compound that was used for the next step without further purification. Yield: 1.00 g (75%); MS (ESI) (M+H)+: 370.2.

Workup

  1. concentrationThe solvent was concentrated
  2. customthe crude product was recovered in EtOAc
  3. washThe organic was washed with water, saturated NaHCO3 solution and brine
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationThe solvent was concentrated

Sources & evidence

ORD record
ord-c9dc110a2d28477ca1b64b96cf5c1811
Source dataset
uspto-grants-2009_06
Patent number
US07550495B2

Reaction notes

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