1,1'-Carbonyldiimidazole → (r)-Tert-butyl 2-(5-(4-carbamoyl-1h-benzimidazol-2-yl)thiophen-2-yl)pyrrolidine-1-carboxylate

HRID 564221Notes

Reaction equation

HRID 564221 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]1[S:14][C:15]([C:18](O)=O)=[CH:16][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.Cl.[NH2:35][C:36]1[C:44]([NH2:45])=[CH:43][CH:42]=[CH:41][C:37]=1[C:38]([NH2:40])=[O:39]>N1C=CC=CC=1.CN(C=O)C>[C:38]([C:37]1[C:36]2[N:35]=[C:18]([C:15]3[S:14][C:13]([C@H:9]4[CH2:10][CH2:11][CH2:12][N:8]4[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:17][CH:16]=3)[NH:45][C:44]=2[CH:43]=[CH:42][CH:41]=1)(=[O:39])[NH2:40]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 534228072,3-Diaminobenzamide dihydrochlorideHCID 66759425(r)-2-(5-Carboxythiophen-2-yl)pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66760174(r)-Tert-butyl 2-(5-(4-carbamoyl-1h-benzimidazol-2-yl)thiophen-2-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of EXAMPLE 16B (2.4 g) in pyridine (20 mL) and DMF (20 mL) was added CDI (1.6 g), and the mixture was stirred at 40° C. for 1 hour. 2,3-Diaminobenzamide dihydrochloride (1.8 g) was added, and the mixture stirred at ambient temperature overnight and concentrated. The concentrate was stirred in of acetic acid (20 mL) at 80° C. for 4 hours and concentrated. The concentrate was partitioned between ethyl acetate and saturated sodium bicarbonate solution, and the extract was washed with water and concentrated. The concentrate was purified by flash chromatography on silica gel with 40-80% ethyl acetate in hexane.

Workup

  1. stirringthe mixture stirred at ambient temperature overnight
  2. concentrationconcentrated
  3. stirringThe concentrate was stirred in of acetic acid (20 mL) at 80° C. for 4 hours
  4. concentrationconcentrated
  5. customThe concentrate was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  6. washthe extract was washed with water
  7. concentrationconcentrated
  8. customThe concentrate was purified by flash chromatography on silica gel with 40-80% ethyl acetate in hexane

Sources & evidence

ORD record
ord-dca1c0030b2c457ebd754654f2b7a5dc
Source dataset
uspto-grants-2011_11
Patent number
US08067613B2

Reaction notes

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