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

HRID 1691473Notes

Reaction equation

HRID 1691473 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])[CH3:36].[C:40]([O:47][CH2:48][CH3:49])(=[O:46])[C:41]([O:43]CC)=O.Cl.C([O-])(O)=O.[Na+]>C1COCC1.C1(C)C=CC=CC=1>[OH:43][C:41]([C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:18])([F:17])[F:19])[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:32])([F:33])[F:31])=[CH:25][CH:24]=3)(=[O:21])=[O:22])[C:6]=2[CH:34]=1)([CH:35]([CH3:37])[CH3:36])[C:40]([O:47][CH2:48][CH3:49])=[O:46]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 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 59618714Ethyl 2-hydroxy-3-methyl-2-[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]butanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

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 (787 mg, 1.28 mmol, intermediate 61) in 2 ml of THF was added a solution of isopropyl magnesium chloride (5.12 ml, 10.24 mmol) in THF (2M) at 0° C. and stirred for 30 min. Then the reaction mixture was added to a solution of diethyl oxalate (4.34 ml, 32 mmol) in 8 mL of toluene and stirred for 30 min. at 0° C. Then the reaction mixture was poured into 3.5 mL of 2 N HCl and 5 mL of ice-water, and the pH was adjusted to pH=7-8 with aqueous NaHCO3. The mixture was extracted with ethyl acetate (3×20 ml) and dried with Na2SO4. The combined organic layers were evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel, eluting with hexane/ethyl acetate (4/1-3/1) to give title compound 509; Mass Spectrum: m/e=634 (M+1). Further elution of the column afforded the title compound 510; Mass Spectrum: m/e=590 (M+1).

Workup

  1. stirringstirred for 30 min. at 0° C
  2. extractionThe mixture was extracted with ethyl acetate (3×20 ml)
  3. dry with materialdried with Na2SO4
  4. customThe combined organic layers were evaporated under reduced pressure
  5. customThe resulting residue was purified by column chromatography on silica gel
  6. washeluting with hexane/ethyl acetate (4/1-3/1)

Sources & evidence

ORD record
ord-8d9fdae20aa44c719eed76477a3a3177
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

Loading…