Ammonium Chloride → (9S)-2,3-Dimethyl-9-phenyl-5,6,7,8,9,10-hexahydroimidazo[1,2-h][1,7]naphthyridin-7-one

HRID 2249711Notes

Reaction equation

HRID 2249711 reaction equation
[NH2:1][C@H:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][C:4]([O:6]CC)=O.[CH3:15][C:16]1[N:17]=[C:18]2[C:23](=O)[CH2:22][CH2:21][CH2:20][N:19]2[C:25]=1[CH3:26].CC(C)([O-])C.[K+].[Cl-].[NH4+]>C1(C)C=CC=CC=1.O1CCCC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[CH3:15][C:16]1[N:17]=[C:18]2[C:23]3[NH:1][C@H:2]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)[CH2:3][C:4](=[O:6])[C:22]=3[CH2:21][CH2:20][N:19]2[C:25]=1[CH3:26]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 915085(S)-Ethyl 3-amino-3-phenylpropanoateHCID 113556692,3-dimethyl-5H,6H,7H,8H-imidazo[1,2-a]pyridin-8-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 69288840(9S)-2,3-Dimethyl-9-phenyl-5,6,7,8,9,10-hexahydroimidazo[1,2-h][1,7]naphthyridin-7-oneYield 88%

Reagents, catalysts & solvents 4

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

9.7 g (51.6 mmol) of ethyl (S)-3-amino-3-phenylpropionate, 8.5 g (51.6 mmol) of 2,3-dimethyl-6,7-dihydro-5H-imidazo[1,2-a]pyridin-8-one and 0.26 g (1.3 mmol) of p-toluenesulphonic acid monohydrate are heated to reflux in 50 ml of toluene using a water separator. After no more water separates, the reaction mixture is cooled to 0° C. and diluted with 100 ml of tetrahydrofuran. 7.24 g (64.5 mmol) of potassium tert-butoxide are then introduced and the mixture is stirred at room temperature for 16 h. 150 ml of saturated ammonium chloride are added to the reaction mixture, the organic phase is removed and the aqueous phase is extracted with 300 ml of ethyl acetate. The combined organic phases are washed with 250 ml of water, dried over sodium sulphate and evaporated. 13.27 g (88%) of the title compound are isolated as a red-brown oil. An analytical sample is obtained by crystallizing with diethyl ether (red solid, m.p. 134° C.).

Workup

  1. customthe organic phase is removed
  2. extractionthe aqueous phase is extracted with 300 ml of ethyl acetate
  3. washThe combined organic phases are washed with 250 ml of water
  4. dry with materialdried over sodium sulphate
  5. customevaporated

Sources & evidence

ORD record
ord-39de779ebc194ab4b2b306cc2142529c
Source dataset
uspto-grants-2008_01
Patent number
US07314935B2

Reaction notes

Loading…