Hydrochloric Acid → 3-[(2-Acetylamino-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 73176Notes

Reaction equation

HRID 73176 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][C:9]=1[N:10]([C:14]([CH:16]1[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH:17]1[N:23]=[N+]=[N-])=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:4].Cl.[H][H].N1C=CC=CC=1.[C:41](OC(=O)C)(=[O:43])[CH3:42]>CO.[Pd].ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][C:9]=1[N:10]([C:14]([CH:16]1[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH:17]1[NH:23][C:41](=[O:43])[CH3:42])=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 597523943-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 597523653-[(2-Acetylamino-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 47%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To 3-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (17.5 mg, 0.04 mmol) in methanol (400 ul) was added concentrated hydrochloric acid (15 ul) followed by 10% palladium on charcoal (4 mg, 0.004 mmol). The reaction vessel was introduced with 20 psi of hydrogen and then stirred at room temperature for 17 hours. The residue was then filtered off through celite, washed with methanol and evaporated to give the crude product. To the crude product in dichloromethane (400 ul) was added pyridine (19 ul, 0.24 mmol), followed by acetic anhydride (15 ul, 0.16 mmol) and a catalytic amount of DMAP. The resulting solution was stirred for 24 hours at room temperature and then quenched with a saturated solution of NaHCO3 (5 ml). The aqueous phase was separated and washed with dichloromethane (2×5 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was then purified by preparative chromatography (60% EtOAc/Hexane) to obtain 8.5 mg (47% for two steps) of 3-[(2-Acetylamino-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester.

Workup

  1. filtrationThe residue was then filtered off through celite
  2. washwashed with methanol
  3. customevaporated
  4. customto give the crude product
  5. stirringThe resulting solution was stirred for 24 hours at room temperature
  6. customquenched with a saturated solution of NaHCO3 (5 ml)
  7. customThe aqueous phase was separated
  8. washwashed with dichloromethane (2×5 ml)
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was then purified by preparative chromatography (60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-158da6bab9f44b2782f21359dda4519a
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

Loading…