Ammonium Hydroxide → 6-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044036Notes

Reaction equation

HRID 2044036 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[N:3]=1.[NH4+].[OH-].C([N:30](C(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.[Li+].[Cl-]>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:30])=[O:8])=[C:4]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:16][CH:17]=2)[N:3]=1

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 574896006-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinic acid

Product 1

HCID 574896016-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 94.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 433294Lithium ChlorideSolvent

Procedure

To a solution of 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinic acid (6.60 g, 18.24 mmol), NH4OH (40.1 mL, 20.07 mmol), and N-ethyl-N-isopropylpropan-2-amine (3.54 g, 27.4 mmol) in DMF (40 mL) was added HATU (13.87 g, 36.5 mmol) at rt. The solution became cloudy but eventually cleared up as the HATU was added. The reaction was completed after 1 h. The reaction mixture was diluted with 10% LiCl and extracted with ethyl acetate three times. The organic extracts was washed with 10% LiCl, water twice, and then concentrated. The light yellow solid was triturated with CH2Cl2 to give 3.8 g. A second trituration gave 1.95 g, and a third trituration gave 462 mg. A total of 6.2 g of 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide was obtained.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate three times
  3. washThe organic extracts was washed with 10% LiCl, water twice
  4. concentrationconcentrated
  5. customThe light yellow solid was triturated with CH2Cl2
  6. customto give 3.8 g
  7. customA second trituration gave 1.95 g
  8. customa third trituration gave 462 mg

Sources & evidence

ORD record
ord-2e71f5b679ed4947b75ee1a4095eb101
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

Loading…