1,2-Dichloroethane → HCID 59511790, compound

HRID 1157449Notes

Reaction equation

HRID 1157449 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:9][C:5]=1[C:6]([OH:8])=[O:7].[NH2:23][CH2:24][C:25]([NH:27][CH:28]([CH3:30])[CH3:29])=[O:26].C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CO>[NH4+:3].[OH-:7].[NH2:3][C:4]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:9][C:5]=1[C:6]([NH:23][CH2:24][C:25](=[O:26])[NH:27][CH:28]([CH3:30])[CH3:29])=[O:8]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 5338492-Amino-N-isopropylacetamideHCID 68521714HCID 68521714, compound

Product 2

HCID 14923Ammonium HydroxideHCID 59511790HCID 59511790, compoundYield 200%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-amino-5-(3-piperidin-1-ylpropoxy)benzoic acid dihydrochloride (1.3 g, 3.7 mmol), 2-amino-N-isopropylacetamide*HCl (INTERMEDIATE I.1) (557 mg, 3.7 mmol) and triethylamine (2.1 mL, 14.8 mmol) in DMF (20 mL) was stirred at room temperature for 10 min. EDC (851 mg, 4.4 mmol) and HOBt (600 mg, 4.4 mmol) were added and stirring continued at room temperature for 16 h. The mixture was partitioned between ethyl acetate (100 mL) and 2N Na2CO3 (aq.) (100 mL) and the aqueous extracted with additional ethyl acetate (2×100 mL). The combined organics were washed with brine (1×100 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by chromatography on silica gel with dichloromethane:methanol: NH4OH (aq.) (160:39:1, v/v) as eluent to provide 2-amino-N-(isopropylcarbamoylmethyl)-5-(3-piperidin-1-ylpropoxy)benzamide (INTERMEDIATE V1.1) (1.4 g, 3.7 mmol, 100%).

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 16 h
  3. customThe mixture was partitioned between ethyl acetate (100 mL) and 2N Na2CO3 (aq.) (100 mL)
  4. extractionthe aqueous extracted with additional ethyl acetate (2×100 mL)
  5. washThe combined organics were washed with brine (1×100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by chromatography on silica gel with dichloromethane

Sources & evidence

ORD record
ord-8e91cf9cd14643fd875cfb996a410ca8
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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