Methanesulfonyl chloride → HCID 22890451, compound

HRID 993134Notes

Reaction equation

HRID 993134 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([O:16][CH3:17])=[CH:4][C:3]=1[CH:18]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=1)[CH2:19][NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22].[CH3:36][S:37](Cl)(=[O:39])=[O:38].Cl.[NH2:42]O.[O-]CC.[Na+]>ClCCl.C(O)C.C(N(CC)CC)C>[CH2:9]([O:8][C:6]1[C:5]([O:16][CH3:17])=[CH:4][C:3]([CH:18]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([C:34]([NH2:42])=[NH:35])=[CH:32][CH:33]=2)[CH2:19][NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])=[C:2]([NH:1][S:37]([CH3:36])(=[O:39])=[O:38])[CH:7]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 443297Hydroxyamine hydrochlorideHCID 2723922Sodium ethoxideHCID 22890466HCID 22890466, compound

Product 1

HCID 22890451HCID 22890451, compoundYield 7.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Propane-1-sulfonic acid [2-(2-amino-4-benzyloxy-5-methoxy-phenyl)-2-(4-cyano-phenylamino)-ethyl]-amide (133 mg, 0.27 mmoles) was dissolved in dichloromethane and triethylamine added (0.05 ml, 0.35 mmoles). The reaction was cooled and methanesulfonyl chloride (0.023 ml, 0.3 mmoles) added dropwise. The reaction was stirred for two hours and the product purified by flash chromatography (hexanes:ethyl acetate, 1:1). The product was then taken-up in ethanol and hydroxylamine hydrochloride (35 mg, 0.5 mmoles) added. Sodium ethoxide (48 mg, 0.7 mmoles was added and the reaction heated for 48 hours. The ethanol was removed and water (4 ml) added. The solid was filtered off and washed with water. The crude product was then taken up in 4 ml of methanol with 0.5 ml acetic acid. Raney Nickel (ca. 50 mg as a suspension in sodium hydroxide, Aldrich) was added and the reaction placed under a hydrogen atmosphere. The reaction was stirred vigorously for 3 hours and the catalyst filtered off. The crude product was submitted to reverse-phase preparative chromatography to yield the final product 4-[1-(4-Benzyloxy-2-methanesulfonylamino-5-methoxy-phenyl)-2-(propane-1-sulfonylamino)-ethylamino]-benzamidine (12 mg): MS (M+H)=590.

Workup

  1. temperatureThe reaction was cooled
  2. customthe product purified by flash chromatography (hexanes:ethyl acetate, 1:1)
  3. temperaturethe reaction heated for 48 hours
  4. customThe ethanol was removed
  5. additionwater (4 ml) added
  6. filtrationThe solid was filtered off
  7. washwashed with water
  8. additionRaney Nickel (ca. 50 mg as a suspension in sodium hydroxide, Aldrich) was added
  9. stirringThe reaction was stirred vigorously for 3 hours
  10. filtrationthe catalyst filtered off

Sources & evidence

ORD record
ord-4e491098bf0241a99208029ddf9a8d75
Source dataset
uspto-grants-2002_10
Patent number
US06472393B1

Reaction notes

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