Water → Ambrisentan

HRID 1854784Notes

Reaction equation

HRID 1854784 reaction equation
[OH:1][C@@H:2]([C:6]([O:19][CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([O-:5])=[O:4].Cl[C@H](C1C=CC(Cl)=CC=1)C[NH3+].CC(C)([O-])C.[K+].[CH3:38][C:39]1[CH:44]=[C:43]([CH3:45])[N:42]=[C:41](S(C)(=O)=O)[N:40]=1.O>CN(C=O)C>[CH3:45][C:43]1[CH:44]=[C:39]([CH3:38])[N:40]=[C:41]([O:1][C@@H:2]([C:6]([O:19][CH3:20])([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:3]([OH:5])=[O:4])[N:42]=1

Participants

6

Reactant 4

HCID 962WaterHCID 27723824,6-Dimethyl-2-methylsulfonylpyrimidineHCID 23665647Potassium tert-butoxideHCID 86668129(R)-2,4-dichlorophenylethyl ammonium (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionate

Product 1

HCID 6918493Ambrisentan

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 25 mL three neck flask with stirring arrangement, (1 gm) (R)-2,4-dichlorophenylethyl ammonium (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionate and (0.726 gm) potassium tertiary butoxide (6.488 mmol) in 10 ml DMF at 25° C. were taken and stirred for 5 min. (0.604 gm) 4,6-dimethyl-2-(methylsulfonyl)pyrimidine (3.244 mmol) was added to the reaction mixture in one lot. The reaction mixture was stirred at room temperature for 6 hours and subsequently dumped into cold water and washed the aqueous layer with toluene. Aqueous layer was collected and acidified with HCl to pH 2. The solid was extracted with ethyl acetate, and wash the ethyl acetate layer with water followed by brine. Dry over sodium sulphate and concentrated on Buchi Rotavapor.

Workup

  1. additionwas added to the reaction mixture in one lot
  2. washwashed the aqueous layer with toluene
  3. customAqueous layer was collected
  4. extractionThe solid was extracted with ethyl acetate
  5. washwash the ethyl acetate layer with water
  6. dry with materialDry over sodium sulphate
  7. concentrationconcentrated on Buchi Rotavapor

Sources & evidence

ORD record
ord-cfa0838c16104336aac10dcfe2d00eec
Source dataset
uspto-grants-2015_02
Patent number
US08962832B2

Reaction notes

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