Dimethylformamide → 1-(Benzyloxycarbonyl)-N-[4-(2-furyl)-5-morpholinothiazol-2-yl]piperidine-4-carboxamide

HRID 337414

Reaction equation

HRID 337414 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.CN(C=O)C.[NH2:29][C:30]1[S:31][C:32]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)=[C:33]([C:35]2[O:36][CH:37]=[CH:38][CH:39]=2)[N:34]=1>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]([NH:29][C:30]2[S:31][C:32]([N:40]3[CH2:41][CH2:42][O:43][CH2:44][CH2:45]3)=[C:33]([C:35]3[O:36][CH:37]=[CH:38][CH:39]=3)[N:34]=2)=[O:19])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic AcidHCID 231441582-Amino-4-(2-furyl)-5-morpholinothiazole2×

Product 1

HCID 231441071-(Benzyloxycarbonyl)-N-[4-(2-furyl)-5-morpholinothiazol-2-yl]piperidine-4-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Benzyloxycarbonylpiperidine-4-carboxylic acid (5.00 g, 19.0 mmol) was dissolved in dichloromethane (80 mL), and thionyl chloride (6.93 mL, 95.0 mmol) and DMF (0.15 mL, 1.90 mmol) were added thereto, followed by stirring under heating and reflux for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in dichloromethane (2 mL). The resulting solution was added to a solution of 2-amino-4-(2-furyl)-5-morpholinothiazole (2.01 g, 8.00 mmol) in pyridine (32 mL) obtained in Step 1 of Example 29, and then N,N-dimethylaminopyridine (97.6 mg, 0.800 mmol) was added thereto, followed by stirring at room temperature for 1 hour. The solvent was distilled away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=1:1 to 1:3) to afford the entitled Compound 43 (4.96 g, 100%).

Workup

  1. temperatureunder heating
  2. temperaturereflux for 3 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutionthe resulting residue was dissolved in dichloromethane (2 mL)
  5. stirringby stirring at room temperature for 1 hour
  6. distillationThe solvent was distilled away under reduced pressure
  7. customthe resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=1:1 to 1:3)

Sources & evidence

ORD record
ord-380679c20ae54fde87e24276a7e48ec9
Source dataset
uspto-grants-2014_11
Patent number
US08889718B2

Linked notes

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