Hydrochloric Acid → HCID 23513725, compound

HRID 353463Notes

Reaction equation

HRID 353463 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]2[N:6]=[C:7]([S:9]([N:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20]C(C)(C)C)=O)[CH2:14][CH2:13]3)(=[O:11])=[O:10])[NH:8][C:4]=2[CH:3]=1.Cl.[N:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:42]=[CH:41][C:37](C(O)=O)=[CH:36][CH:35]=2)=[CH:30][CH:29]=1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl.CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]2[N:6]=[C:7]([S:9]([N:12]3[CH2:13][CH2:14][N:15]([C:18](=[O:20])[C:37]4[CH:36]=[CH:35][C:34]([C:31]5[CH:30]=[CH:29][N:28]=[CH:33][CH:32]=5)=[CH:42][CH:41]=4)[CH2:16][CH2:17]3)(=[O:10])=[O:11])[NH:8][C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 15208114-(Pyridin-4-yl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23513721HCID 23513721, compound

Product 1

HCID 23513725HCID 23513725, compoundYield 35.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-(t-butyloxycarbonyl)piperazine (860 mg, 2.15 mmol) in dichloromethane/methanol (15 ml of 1:1) was treated with an excess of hydrogen chloride gas as a saturated solution in ethyl acetate. After stirring for 4 hrs. the solvent was removed in vacuo and the residue dried under high vacuum. This was then suspended in DMF and treated sequentially with 4-(4-pyridyl)benzoic acid (428 mg, 2.15 mmol), triethylamine (0.6 ml, 4.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC, 495 mg, 2.68 mmol). After stirring overnight the solvent was removed in vacuo and the residue taken up in dichloromethane (50 ml). This was washed sequentially with water, saturated sodium bicarbonate solution, water and brine. Evaporation of the solvent gave a residue which was purified by chromatography (MPLC on Merck Art 9385 silica, gradient eluting with ethyl acetate containing 0-8.0% methanol) to give 1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-[4-(4-pyridyl)benzoyl]piperazine as colourless crystals (370 mg) from ethanol, m.p. 242-244° C., 1H NMR (d6DMSO) 3.0-3.4 ppm (broad s, 4H), 3.4-3.8 ppm (broad s, 4H), 7.4 ppm (d, 1H), 7.5 ppm (d, 2H), 7.6-7.8 ppm (m, 4H), 7.85 ppm 2H), 8.6 ppm (d, 2H), 14.0 ppm (broad s, 1H); MS (M+H)+ 482/484.

Workup

  1. customthe solvent was removed in vacuo
  2. customthe residue dried under high vacuum
  3. stirringAfter stirring overnight the solvent
  4. customwas removed in vacuo
  5. washThis was washed sequentially with water, saturated sodium bicarbonate solution, water and brine
  6. customEvaporation of the solvent
  7. customgave a residue which
  8. customwas purified by chromatography (MPLC on Merck Art 9385 silica, gradient eluting with ethyl acetate containing 0-8.0% methanol)

Sources & evidence

ORD record
ord-dc284c121d394319b993260eeba670dc
Source dataset
uspto-grants-2004_06
Patent number
US06753331B1

Reaction notes

Loading…