1,2-Dichloroethane → 4-(1-(2-Ethyl-4-methyl-5-(7-methyl-3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2-yl)benzoyl)piperidin-4-yl)benzonitrile

HRID 541435Notes

Reaction equation

HRID 541435 reaction equation
[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[NH:17][C:16]3[CH2:18][O:19][CH2:20][CH:21]([CH3:22])[C:15]=3[N:14]=2)=[CH:8][C:4]=1[C:5](O)=[O:6])[CH3:2].Cl.[NH:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1.C(Cl)CCl>CN(C=O)C.C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[NH:17][C:16]3[CH2:18][O:19][CH2:20][CH:21]([CH3:22])[C:15]=3[N:14]=2)=[CH:8][C:4]=1[C:5]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1)=[O:6])[CH3:2]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 682890962-Ethyl-4-methyl-5-(7-methyl-3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2-yl)benzoic acid2×

Product 1

HCID 682890834-(1-(2-Ethyl-4-methyl-5-(7-methyl-3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2-yl)benzoyl)piperidin-4-yl)benzonitrileYield 7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

Into around-bottom flask, was placed a solution of 2-ethyl-4-methyl-5-(7-methyl-3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2-yl)benzoic acid (compound 400.3, 30 mg, 0.10 mmol, 1.0 equiv) in DMF/DCM (5/5 mL). 4-(Piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 50 mg, 0.22 mmol, 2.2 equiv), EDC (40 mg, 2.0 equiv) and 4-dimethylaminopyridine (28 mg, 2.0 equiv) were added. The resulting solution was stiffed overnight at 25° C., then quenched with water (10 mL). The mixture was extracted with ethyl acetate (3×5 mL), and the combined organic layers was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatraphy with ethyl acetate/petroleum ether (2:1) as the eluent to obtain the title compound as a light yellow solid (3.2 mg, 7%). m/z (ES+) 469 (M+H)+.

Workup

  1. customInto around-bottom flask, was placed
  2. customquenched with water (10 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×5 mL)
  4. dry with materialthe combined organic layers was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatraphy with ethyl acetate/petroleum ether (2:1) as the eluent

Sources & evidence

ORD record
ord-3c0dcf2bce3f46b99b7078a847fbb377
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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