Isobutyl chloroformate → HCID 71147037, compound

HRID 1426432Notes

Reaction equation

HRID 1426432 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:18][CH2:17][CH2:16][C@H:12]2[C:13]([OH:15])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(Cl)(=O)OCC(C)C.[NH2:27][C:28]1[CH:32]=[C:31]([Br:33])[S:30][C:29]=1[C:34]([NH2:36])=[O:35].C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[Br:33][C:31]1[S:30][C:29]([C:34](=[O:35])[NH2:36])=[C:28]([NH:27][C:13](=[O:15])[C@@H:12]2[CH2:16][CH2:17][CH2:18][N:11]2[C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=2)[CH:32]=1

Participants

8

Reactant 4

HCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 219758623-Amino-5-bromothiophene-2-carboxamideHCID 25631141HCID 25631141, compound

Product 1

HCID 71147037HCID 71147037, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-[4-(methylsulfonyl)phenyl]proline (512 mg) and triethylamine (0.314 mL) in tetrahydrofuran (10 mL) was added 2-methylpropyl chlorocarbonate (0.259 mL) at 0° C., and the mixture was stirred at room temperature for 30 min. Thereafter, to the reaction system was added 3-amino-5-bromothiophene-2-carboxamide (200 mg) produced in Example 1, step D, and the mixture was stirred at 60° C. for 19 hr. Ethyl acetate (20 mL) and aqueous sodium hydrogen carbonate (10 mL) were added to the reaction mixture, and the separated organic layer was washed with brine (5 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the object fraction was concentrated under reduced pressure to give N-(5-bromo-2-carbamoylthiophen-3-yl)-1-[4-(methylsulfonyl)phenyl]prolinamide as a pale-yellow amorphous solid. To a solution of N-(5-bromo-2-carbamoylthiophen-3-yl)-1-[4-(methylsulfonyl)phenyl]prolinamide produced above in ethanol (5 mL) was added 2M aqueous sodium hydroxide solution (2.83 mL), and the mixture was stirred at 70° C. for 10 hr. The reaction mixture was neutralized with 6M hydrochloric acid (0.6 mL) under ice-cooling, and water (2 mL) was added dropwise at room temperature. The precipitated solid was collected by filtration to give the title compound (208 mg) as a pale-yellow solid.

Workup

  1. stirringthe mixture was stirred at 60° C. for 19 hr
  2. washthe separated organic layer was washed with brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationInsoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  7. concentrationthe object fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2486be8ebd554ad7857c3052487ae971
Source dataset
uspto-grants-2015_01
Patent number
US08933069B2

Reaction notes

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