Water → Befetupitant

HRID 379430Notes

Reaction equation

HRID 379430 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:13]([CH3:18])([CH3:17])[C:14](Cl)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:21][NH:22][C:23]1[CH:24]=[N:25][C:26]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:27][C:28]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35].C(N(C(C)C)C(C)C)C.O>ClCCl>[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:13]([CH3:18])([CH3:17])[C:14]([N:22]([CH3:21])[C:23]2[CH:24]=[N:25][C:26]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:27][C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 112671412-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropanoyl chlorideHCID 11437557Methyl-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-amine

Product 1

HCID 6450815BefetupitantYield 64.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 1.2 g (3.8 mMol) 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride and 0.5 ml dichloromethane were added dropwise over 15 minutes at 0° C. to a solution of 1.0 g (3.5 mMol) methyl-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-amine and 0.85 ml (4.9 mMol) N-ethyl-di-isopropylamine in 7.0 ml dichloromethane. The reaction mixture was stirred 2.5 hours at 0° C., poured onto 8 ml deionized water and stirred further 30 minutes at room temperature. The phases were separated and the aqueous phase extracted with dichloromethane. The organic extracts were washed with deionized water, aqueous sodium hydroxide 2% and aqueous sodium bicarbonate 5%, dried (Na2SO4) and concentrated under reduced pressure. The residue was crystallized from ethanol at −20° C. to yield 1.27 g (64%) 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide as a white powder. Concentration of the mother-liquors gave 0.77 g of a slowly crystallizing brown oil which can be further purified.

Workup

  1. additionpoured onto 8 ml
  2. stirringstirred further 30 minutes at room temperature
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted with dichloromethane
  5. washThe organic extracts were washed with deionized water, aqueous sodium hydroxide 2% and aqueous sodium bicarbonate 5%
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was crystallized from ethanol at −20° C.

Sources & evidence

ORD record
ord-a75bae8872a74e71acb2d19ea0cc707b
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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