Ethyl Acetate → Tert-butyl 3-(6-{(3,5-bis-trifluoromethyl-benzyl)-[2-(butyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-4-ylamino)-propionate

HRID 604092Notes

Reaction equation

HRID 604092 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[N:26]([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:27][CH3:28])[C:8]1[CH:13]=[C:12](Cl)[N:11]=[CH:10][N:9]=1.Cl.[C:43]([O:47][C:48](=[O:52])[CH2:49][CH2:50][NH2:51])([CH3:46])([CH3:45])[CH3:44].C(N(C(C)C)C(C)C)C.C(OCC)(=O)C>C1(C)C=CC=CC=1>[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[N:26]([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:27][CH3:28])[C:8]1[N:9]=[CH:10][N:11]=[C:12]([NH:51][CH2:50][CH2:49][C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:52])[CH:13]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 86626845(3,5-Bis-trifluoromethyl-benzyl)-[2-(butyl-ethyl-amino)-5-trifluoromethyl-benzyl]-(6-chloropyrimidin-4-yl)-amine

Product 1

HCID 86626846Tert-butyl 3-(6-{(3,5-bis-trifluoromethyl-benzyl)-[2-(butyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-4-ylamino)-propionateYield 19.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-[2-(butyl-ethyl-amino)-5-trifluoromethyl-benzyl]-(6-chloropyrimidin-4-yl)-amine (300 mg) is dissolved in toluene (5 ml), and thereto are added 3-aminopropionic acid tert-butyl ester hydrochloride (888 mg) and N-ethyldiisopropylamine (1.7 ml), and the mixture is stirred at 120° C. overnight. To the reaction solution are added ethyl acetate and a 1N-hydrochloric acid, and the mixture is separated. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (hexane:ethyl acetate=9:1→3:1) to give tert-butyl 3-(6-{(3,5-bis-trifluoromethyl-benzyl)-[2-(butyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-4-ylamino)-propionate (70 mg). MS (m/z): 722 [M+H]+

Workup

  1. customa 1N-hydrochloric acid, and the mixture is separated
  2. washThe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (hexane:ethyl acetate=9:1→3:1)

Sources & evidence

ORD record
ord-d941789e903847bba6c3d964d048cb03
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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