Hydrochloric Acid → Ethyl 6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carboxylate

HRID 1691475Notes

Reaction equation

HRID 1691475 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[CH:34]=1.[CH:35]([Mg]Cl)([CH3:37])C.Cl.[C:41]([O-])([OH:43])=[O:42].[Na+]>C1COCC1>[F:31][C:30]([F:33])([F:32])[O:29][C:26]1[CH:27]=[CH:28][C:23]([S:20]([N:7]2[C:6]3[CH:34]=[C:2]([C:41]([O:43][CH2:35][CH3:37])=[O:42])[CH:3]=[CH:4][C:5]=3[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8]2)(=[O:22])=[O:21])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 596187318-Iodo-6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×HCID 178418918HCID 178418918, compound

Product 1

HCID 59618615Ethyl 6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 8-iodo-6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (380 mg, 0.618 mmol, intermediate 61) in 2 ml of THF was added a solution of isopropyl magnesium chloride (1.54 ml, 3.08 mmol) in THF (2M) at 0° C. and the solution was stirred for 30 min at 0° C. Then the reaction mixture was added to a solution of ethyl cyanidocarbonate in 3 mL of THF and stirred for 30 min at 0° C. The reaction mixture was poured into 2 mL of 2N HCl and 5 mL of ice-water, and the pH was adjusted to 7-8 with aqueous NaHCO3 at 0° C. The solution was extracted with ethyl acetate (3×20 ml), and the combined organic extracts were dried over Na2SO4. The solution was concentrated under reduced pressure and the residue was purified by silica gel chromatography using with hexane/ethyl acetate (6/1) to give the title compound as a white solid; Mass Spectrum: m/e=562 (M+1).

Workup

  1. stirringstirred for 30 min at 0° C
  2. extractionThe solution was extracted with ethyl acetate (3×20 ml)
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. concentrationThe solution was concentrated under reduced pressure
  5. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-bac094e958dd4197b2700cc17616513f
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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