Dicyclohexylcarbodiimide → HCID 70051543, compound

HRID 1885299Notes

Reaction equation

HRID 1885299 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH3:13])[CH:3]=1.[NH2:14][CH:15]1[CH2:19][CH:18]([CH2:20][OH:21])[N:17]([CH2:22][CH3:23])[CH2:16]1.O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.O1CCCC1>[ClH:11].[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([NH:14][CH:15]2[CH2:19][CH:18]([CH2:20][OH:21])[N:17]([CH2:22][CH3:23])[CH2:16]2)=[O:8])=[C:4]([O:12][CH3:13])[CH:3]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 19880424HCID 19880424, compound

Product 1

HCID 70051543HCID 70051543, compoundYield 116.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Into a reaction vessel, were placed 1.00 g of 4-amino-5-chloro-2-methoxy benzoic acid, 0.75 g of 3-amino-1-ethyl-5-hydroxymethyl pyrrolidine, 0.83 g of 1-hydroxy-1H-benzotriazole monohydrate, 1.13 g of dicyclohexyl carbodiimide (DCC), 15 ml of tetrahydrofuran (THF) and 2 ml of dimethyl formamide (DMF), and thus obtained mixture was stirred at room temperature for 14 hours. Thereafter, the precipitated dicyclohexyl carbonyl urea (DCU) was removed off, the filtrate was concentrated under reduced pressure and the residue was added with a dilute hydrogen chloride solution and washed twice with chloroform. The aqueous solution was alkalized with sodium bicarbonate and then extracted twice with chloroform. The organic extract was washed with a saturated aqueous saline solution and dried over magnesium sulfate. The extract was concentrated under reduced pressure and the residue was added with toluene, from which crystalline material was precipitated and separated. This was treated in isopropyl alcohol with HCl gas to convert to its hydrochloride and the thus formed hydrochloride precipitate was separated to obtain 1.05 g of 4-amino-5-chloro-2-methoxy-N-(1-ethyl-5-hydroxymethyl pyrrolidin-3-yl) benzamide hydrochloride (Compound of Example 1 in Table 1) M.p. 162° to 165° C.

Workup

  1. customInto a reaction vessel, were placed
  2. customThereafter, the precipitated dicyclohexyl carbonyl urea (DCU) was removed off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionthe residue was added with a dilute hydrogen chloride solution
  5. washwashed twice with chloroform
  6. extractionextracted twice with chloroform
  7. extractionThe organic extract
  8. washwas washed with a saturated aqueous saline solution
  9. dry with materialdried over magnesium sulfate
  10. concentrationThe extract was concentrated under reduced pressure
  11. additionthe residue was added with toluene, from which crystalline material
  12. customwas precipitated
  13. customseparated
  14. additionThis was treated in isopropyl alcohol with HCl gas
  15. customthe thus formed hydrochloride precipitate was separated

Sources & evidence

ORD record
ord-9d2b2d7a48cd41e6a6f09487e9727322
Source dataset
uspto-grants-1992_09
Patent number
US05143935

Reaction notes

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