Methanesulfonyl chloride → HCID 10674163, compound

HRID 1596376Notes

Reaction equation

HRID 1596376 reaction equation
[CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:10]([CH2:12][N:13]1[C:19]3[C:20]([CH3:24])=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([CH2:25]O)=[N:16][CH:15]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=3)=[O:29])[C:14]1=[O:38])=[O:11])[CH2:2]2.C(N(C(C)C)CC)(C)C.[CH3:48][S:49](Cl)(=O)=O.[Na]>C(Cl)Cl.O1CCCC1.C(OCC)(=O)C.CO.C(Cl)(Cl)Cl>[CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:10]([CH2:12][N:13]1[C:19]3[C:20]([CH3:24])=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([CH2:25][S:49][CH3:48])=[N:16][CH:15]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=3)=[O:29])[C:14]1=[O:38])=[O:11])[CH2:2]2

Participants

10

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 10815755HCID 10815755, compound

Product 1

HCID 10674163HCID 10674163, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

To a mixture of N-[(3RS)-1-(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl-5-hydroxymethyl-9-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-N′-(3-methylphenyl)urea (147 mg) and diisopropylethylamine (55.1 mg) in methylene chloride (2 ml) was added dropwise a solution of methanesulfonyl chloride (48.7 mg) in methylene chloride (1 ml) under stirring and cooling at 0-5° C. in an ice-bath. The mixture was stirred for 1.5 hours under the same conditions. The reaction mixture was evaporated in vacuo to afford a residue, which was dissolved in tetrahydrofuran (2 ml) and cooled in an ice-bath. To the solution prepared above was added 15% aqueous solution of sodium methylmercaptide (0.5 g). The mixture was stirred under cooling for 0.5 hour and at ambient temperature for 2 hours. The reaction mixture was evaporated in vacuo to afford a residue, which was dissolved in ethyl acetate and washed with water twice. The separated organic layer was dried over magnesium sulfate and evaporated in vacuo to afford an amorphous mass, which was subjected to preparative thin-layer chromatography on silica gel developing with a mixture of chloroform and methanol (10:1) to give N-[(3RS)-1-(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl-5-methylthiomethyl-9-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-N′-(3-methyphenyl)urea as an amorphous mass. This was triturated in diisopropyl ether and collected by filtration to give a crystalline powder (71.9 mg, 41.7% yield).

Workup

  1. stirringThe mixture was stirred for 1.5 hours under the same conditions
  2. customThe reaction mixture was evaporated in vacuo
  3. customto afford a residue, which
  4. temperaturecooled in an ice-bath
  5. customTo the solution prepared
  6. stirringThe mixture was stirred
  7. temperatureunder cooling for 0.5 hour and at ambient temperature for 2 hours
  8. customThe reaction mixture was evaporated in vacuo
  9. customto afford a residue, which
  10. washwashed with water twice
  11. dry with materialThe separated organic layer was dried over magnesium sulfate
  12. customevaporated in vacuo
  13. customto afford an amorphous mass, which

Sources & evidence

ORD record
ord-39a2d6bb3bae44f194cef69105c599e3
Source dataset
uspto-grants-2001_09
Patent number
US06291452B1

Reaction notes

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