Trifluoroacetic acid → (2S)-1-(1H-indol-3-ylmethyl)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one

HRID 72388Notes

Reaction equation

HRID 72388 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C@@:9]1([C:42]([F:45])([F:44])[F:43])[CH2:24][N:12]2[C:13](=[O:23])[CH:14]=[C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:16]=[C:11]2[N:10]1[CH2:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28](C(OC(C)(C)C)=O)[CH:27]=1>C(Cl)Cl>[NH:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:26]([CH2:25][N:10]2[C:11]3=[N:16][C:15]([N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)=[CH:14][C:13](=[O:23])[N:12]3[CH2:24][C@@:9]2([CH3:8])[C:42]([F:44])([F:45])[F:43])=[CH:27]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67774832HCID 67774832, compound

Product 1

HCID 50899710(2S)-1-(1H-indol-3-ylmethyl)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)oneYield 46.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1 ml of trifluoroacetic acid is added to a solution of 200 mg of 2-methylpropan-2-yl 3-{[(2S)-2-methyl-7-(morpholin-4-yl)-5-oxo-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-1(5H)-yl]methyl}-1H-indole-1-carboxylate in 3 ml of methylene chloride. After an overnight period at a temperature in the region of 20° C., the reaction mixture is concentrated to dryness under reduced pressure. After purification by preparative LC MS (method D), the acetonitrile is concentrated and then the aqueous phase is extracted with ethyl acetate. The organic phase is successively washed with a saturated aqueous solution of sodium bicarbonate, twice with water and once with a saturated aqueous solution of sodium chloride. The resulting organic phase is dried over anhydrous magnesium sulphate, filtered and then concentrated to dryness under reduced pressure. The residue it taken up with water and then lyophilized. 75 mg of (2S)-1-(1H-indol-3-ylmethyl)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one are thus obtained in the form of a pinkish-coloured lyophilisate, the characteristics of which are the following:

Workup

  1. concentrationthe reaction mixture is concentrated to dryness under reduced pressure
  2. customAfter purification by preparative LC MS (method D)
  3. concentrationthe acetonitrile is concentrated
  4. extractionthe aqueous phase is extracted with ethyl acetate
  5. washThe organic phase is successively washed with a saturated aqueous solution of sodium bicarbonate, twice with water and once with a saturated aqueous solution of sodium chloride
  6. dry with materialThe resulting organic phase is dried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-df18603c9afd4b889bd75284e93ebc43
Source dataset
uspto-grants-2014_09
Patent number
US08828997B2

Reaction notes

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