Betahistine → HCID 9893538, compound

HRID 2305222Notes

Reaction equation

HRID 2305222 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([C@@H:18]3[CH2:22][CH2:21][CH2:20][C@H:19]3[CH2:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27](O)=[O:28])[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:33][NH:34][CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.CCOC(C)=O>[CH3:33][N:34]([CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1)[C:27](=[O:28])[C:26]1[CH:30]=[CH:31][CH:32]=[C:24]([CH2:23][C@@H:19]2[CH2:20][CH2:21][CH2:22][C@H:18]2[C:9]2[O:10][C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)[CH:25]=1

Participants

6

Reactant 3

HCID 2366BetahistineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11327698HCID 11327698, compound

Product 1

HCID 9893538HCID 9893538, compoundYield 91.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-{[(1S,2R)-2-(4,5-diphenyloxazol-2-yl)-1-cyclopentyl]methyl}benzoic acid (120 mg, 0.284 mmol) and 2-(2-methylaminoethyl)pyridine (0.047 ml, 0.341 mmol) in DMF (5 ml) was added 1-hydroxybenzotrioxazole (58 mg, 0.426 mmol) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (109 mg, 0.568 mmol). After stirring the mixture at room temperature for 2 hours, the reaction mixture was diluted with EtOAc (30 ml), washed with water, saturated sodium hydrogencarbonate solution, water, and brine. The resultant mixture was dried over magnesium sulfate, and evaporated in vacuo. The resultant residue was purified by silica gel column chromatography (methylene chloride: MeOH, 15:1 elution), then treated with 4N hydrogen chloride in EtOAc (1ml) to give N-methyl-N-[2-(pyridin-2-yl)ethyl]-3-{[(1S,2R)-2-(4,5-diphenyloxazol-2-yl)-1-cyclopentyl]methyl}benzamide (140.9 mg, 86%).

Workup

  1. washwashed with water, saturated sodium hydrogencarbonate solution, water, and brine
  2. dry with materialThe resultant mixture was dried over magnesium sulfate
  3. customevaporated in vacuo
  4. customThe resultant residue was purified by silica gel column chromatography (methylene chloride: MeOH, 15:1 elution)
  5. additiontreated with 4N hydrogen chloride in EtOAc (1ml)

Sources & evidence

ORD record
ord-56ddfd37e4934a9e99369d0da3011325
Source dataset
uspto-grants-2002_08
Patent number
US06437146B1

Reaction notes

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