Piperidine → 4-(3-Chloro-phenyl)-2-(6-piperidin-1-ylmethyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid amide

HRID 1667693Notes

Reaction equation

HRID 1667693 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:20]4[CH:21]=[C:22]([CH:25]=O)[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1.[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl-].[NH4+].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:20]4[CH:21]=[C:22]([CH2:25][N:27]5[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]5)[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 5049666Sodium triacetoxyborohydrideHCID 866428104-(3-Chloro-phenyl)-2-(6-formyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid amide

Product 1

HCID 468349034-(3-Chloro-phenyl)-2-(6-piperidin-1-ylmethyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 0.150 g (0.39 mmole) of 4-(3-chloro-phenyl)-2-(6-formyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid amide (I.2a), 0.078 mL of piperidine, 0.414 g of sodium triacetoxyborohydride and 5 mL of dichloromethane was stirred at room temperature for 24 hours, after which 1 mL of saturated aqueous ammonium chloride solution was added. The mixture was stirred at room temperature for 30 minutes, made basic by addition of saturated potassium carbonate solution and partitioned between 30 mL of dichloromethane and 30 mL of dilute potassium carbonate solution. The aqueous layer was extracted twice with 30 mL of dichloromethane. The combined dichloromethane layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was triturated with dichloromethane to give a pink solid. Further purification by SFC (methanol) gave 0.050 g of 4-(3-chloro-phenyl)-2-(6-piperidin-1-ylmethyl-benzoimidazol-1-yl)-thiazole-5-carboxylic acid amide (I.8) as a yellow solid. MH+/Z=452

Workup

  1. stirringThe mixture was stirred at room temperature for 30 minutes
  2. custompartitioned between 30 mL of dichloromethane and 30 mL of dilute potassium carbonate solution
  3. extractionThe aqueous layer was extracted twice with 30 mL of dichloromethane
  4. washThe combined dichloromethane layers were washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with dichloromethane
  9. customto give a pink solid
  10. customFurther purification by SFC (methanol)

Sources & evidence

ORD record
ord-4e75a87a9c214e63af7528e411099b1b
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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