Hydrochloric Acid → HCID 136333950, compound

HRID 1409064Notes

Reaction equation

HRID 1409064 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7](=[O:9])[NH2:8])=[C:4]([NH:10][C:11]([C@@H:13]2[CH2:17][CH:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:15][N:14]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=O)[CH:3]=1.[OH-].[Na+].Cl>C(O)C>[Br:1][C:2]1[S:6][C:5]2[C:7](=[O:9])[NH:8][C:11]([C@@H:13]3[CH2:17][CH:16]([N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)[CH2:15][N:14]3[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:10][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86676227HCID 86676227, compound

Product 1

HCID 136333950HCID 136333950, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

In the same manner as in Example 11, step A, tert-butyl (2S)-2-[(5-bromo-2-carbamoylthiophen-3-yl)carbamoyl]-4-piperidin-1-ylpyrrolidine-1-carboxylate was obtained as a pale-brown amorphous solid (132 mg) from 3-amino-5-bromothiophene-2-carboxamide (200 mg) produced in Example 1, step D and 1-(tert-butoxycarbonyl)-4-piperidin-1-yl-L-proline (270 mg) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (413 mg) and N-ethyl-N-(1-methylethyl)propan-2-amine (0.316 mL) and N,N-dimethylformamide (5.0 mL). To tert-butyl (2S)-2-[(5-bromo-2-carbamoylthiophen-3-yl)carbamoyl]-4-piperidin-1-ylpyrrolidine-1-carboxylate produced above were added 2M aqueous sodium hydroxide solution (0.52 mL) and ethanol (1.0 mL), and the mixture was stirred at 70° C. for 2 hr. The reaction system was neutralized with 1M hydrochloric acid at 0° C. The mixture was extracted with ethyl acetate, and the mixture was washed with brine, and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (63 mg) as a pale-brown amorphous solid.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washthe mixture was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customInsoluble material was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2e0988d8b5f24b6e93b100610ef646ea
Source dataset
uspto-grants-2014_12
Patent number
US08921354B2

Reaction notes

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