1,2-Diaminocyclohexane → (S)-4-(1H-benzo[d]imidazol-6-yl)-5-(4-propoxyphenyl)morpholin-3-one

HRID 452096Notes

Reaction equation

HRID 452096 reaction equation
F[C:2](F)(F)C([O-])=O.[CH2:8]([O:11][C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]2[NH:23][C:22](=[O:24])[CH2:21][O:20][CH2:19]2)=[CH:14][CH:13]=1)[CH2:9][CH3:10].I[C:26]1[CH:27]=[C:28]([NH2:33])[C:29]([NH2:32])=[CH:30][CH:31]=1.[F-].[Cs+].C1(N)CCCCC1N>[Cu]I>[NH:33]1[C:28]2[CH:27]=[C:26]([N:23]3[C@@H:18]([C:15]4[CH:14]=[CH:13][C:12]([O:11][CH2:8][CH2:9][CH3:10])=[CH:17][CH:16]=4)[CH2:19][O:20][CH2:21][C:22]3=[O:24])[CH:31]=[CH:30][C:29]=2[N:32]=[CH:2]1

Participants

7

Reactant 5

HCID 46101,2-DiaminocyclohexaneHCID 25953Cesium fluorideHCID 84468TrifluoroacetateHCID 112070494-Iodobenzene-1,2-diamineHCID 58229161(S)-5-(4-propoxyphenyl)morpholin-3-one

Product 1

HCID 51030217(S)-4-(1H-benzo[d]imidazol-6-yl)-5-(4-propoxyphenyl)morpholin-3-one

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
95 °C

Procedure

The final product was synthesized as trifluoroacetate salt starting from (S)-5-(4-propoxyphenyl)morpholin-3-one (0.044 g, 0.19 mmol), 4-iodobenzene-1,2-diamine (0.044 g, 0.19 mmol), copper(I) iodide (0.004 g, 0.019 mmol), cesium fluoride (0.058 g, 0.38 mmol), cyclohexane-1,2-diamine (0.0025 mL, 0.019 mmol). The solids were given together in a reaction flask and the flask was purged with argon. A solution of cyclohexane-1,2-diamine in 2 mL dioxane was added to the flask. The reaction was stirred at 95° C. for 4 days, before the reaction was cooled down to 45° C. and filtered through a pad of celite. The pad was washed with warm dichloromethane and the solution was concentrated under reduced pressure. The intermediate product was purified via FPLC using a chloroform-methanol gradient (0→10%) Yield: 0.01 g (15%); MS m/z 342.2 (M+H)+

Workup

  1. customThe solids were given together in a reaction flask
  2. customthe flask was purged with argon
  3. additionA solution of cyclohexane-1,2-diamine in 2 mL dioxane was added to the flask
  4. temperaturewas cooled down to 45° C.
  5. filtrationfiltered through a pad of celite
  6. washThe pad was washed with warm dichloromethane
  7. concentrationthe solution was concentrated under reduced pressure
  8. customThe intermediate product was purified via FPLC

Sources & evidence

ORD record
ord-0fde2d7b2c8249a391872e62a29b193e
Source dataset
uspto-grants-2013_07
Patent number
US08486940B2

Reaction notes

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