1,2-Dichloroethane → HCID 178522419, compound

HRID 1012082Notes

Reaction equation

HRID 1012082 reaction equation
CO[C:3](=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH2:11][CH2:12][N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.[OH-].[Li+].Cl.[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[C:31]1[C:35]([NH2:36])=[CH:34][NH:33][N:32]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.O.O.CN(C=O)C>[NH:24]1[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N:22]=[C:23]1[C:31]1[C:35]([NH:36][C:3](=[O:18])[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[O:10][CH2:11][CH2:12][N:13]2[CH2:14][CH2:15][CH2:16][CH2:17]2)=[CH:34][NH:33][N:32]=1

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 757711-HydroxybenzotriazoleHCID 59733402Methyl 2-(2-(pyrrolidin-1-yl)ethoxy)benzoateHCID 178508052HCID 178508052, compound

Product 1

HCID 178522419HCID 178522419, compoundYield 30.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

2-(2-Pyrrolidin-1-yl-ethoxy)-benzoic acid methyl ester (125 mg, 0.50 mmol) and lithium hydroxide (21 mg, 0.50 mmol) were dissolved in THF/H2O (1:1, 2 ml) and the mixture stirred at ambient temperature for 20 h. The reaction mixture was reduced in vacuo and azeotroped with toluene (3×5 ml) to give a white solid, which was dissolved in water (1 ml) and acidified with 2 M aqueous HCl (1 ml). The resulting solution was reduced in vacuo and azeotroped with toluene (3×5 ml) to give a pale yellow gel, which was combined with 3-(1H-benzimidazol-2-yl)-1H-pyrazol-4-ylamine (100 mg, 0.50 mmol), EDC (116 mg, 0.60 mmol) and HOBt (81 mg, 0.60 mmol) and stirred at ambient temperature in DMF (3 ml) for 20 h. The reaction mixture was reduced in vacuo and purified by flash column chromatography [SiO2, CH2Cl2/MeOH (95:5, 87.5:12.5) then 120 DMAW] to give N-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-2-(2-pyrrolidin-1-yl-ethoxy)-benzamide (63 mg, 30%) as a pale pink solid. (LC/MS: Rt 2.08, [M+H]+ 417.11).

Workup

  1. customazeotroped with toluene (3×5 ml)
  2. customto give a white solid, which
  3. customazeotroped with toluene (3×5 ml)
  4. customto give a pale yellow gel, which
  5. custompurified by flash column chromatography [SiO2, CH2Cl2/MeOH (95:5, 87.5:12.5)

Sources & evidence

ORD record
ord-45ddd1fdab6b495aa8c12d8367e0539a
Source dataset
uspto-grants-2011_07
Patent number
US07977477B2

Reaction notes

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