Methanesulfonyl chloride → HCID 76540325, compound

HRID 2117267Notes

Reaction equation

HRID 2117267 reaction equation
[O:1]=[C:2]1[C:8](=[CH:9][OH:10])[C:7](=[O:11])[N:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[CH:4][N:3]1[CH2:18][C:19]([N:21]([CH:30]([CH3:32])[CH3:31])[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)=[O:20].[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:1]=[C:2]1[C:8](=[CH:9][O:10][S:34]([CH3:33])(=[O:36])=[O:35])[C:7](=[O:11])[N:6]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:5]=[CH:4][N:3]1[CH2:18][C:19]([N:21]([CH:30]([CH3:32])[CH3:31])[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1)=[O:20]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 69224175HCID 69224175, compound

Product 1

HCID 76540325HCID 76540325, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-[2,4-dioxo-3-(hydroxymethylene)-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide (−12r, 0.500 g) in CH2Cl2 (10 mL) under argon was treated with methanesulfonyl chloride (0.266 mL) and diisopropylethylamine (0.598 mL). After several minutes, the reaction was transferred to a separatory funnel and washed with aqueous 1N NaHSO4. The aqueous layer was back-extracted with CH2Cl2. The combined organic layers were dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified on flash grade silica gel eluting with 2:3 ethyl acetate/hexane. Fractions containing the product were combined, evaporated in vacuo and triturated with hexane. Hexane was removed in vacuo and the residual solid was dried under high vacuum to provide 2-[2,4-dioxo-3-(methanesulfonyloxymethylene)-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide (12s, 0.502 g) as a solid. The product was contaminated with approximately 40% of 2-[2,4-dioxo-3-methylene-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide which reacted equally well in the subsequent steps. 1H NMR (300 MHz, CDCl3) 1.10 (d, J=7 Hz, 6H), 3.15 (s, 3H), 3.89 (s, 3H), 3.96 (d, J=2 Hz, 2H), 4.92 (m, 4H), 6.03 (m, 2H), 7.00 (m, 2H), 7.18 (m, 2H), 7.40 (m, 5H).

Workup

  1. waitAfter several minutes
  2. customthe reaction was transferred to a separatory funnel
  3. washwashed with aqueous 1N NaHSO4
  4. extractionThe aqueous layer was back-extracted with CH2Cl2
  5. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified on flash grade silica gel eluting with 2:3 ethyl acetate/hexane
  9. additionFractions containing the product
  10. customevaporated in vacuo
  11. customtriturated with hexane
  12. customHexane was removed in vacuo
  13. customthe residual solid was dried under high vacuum

Sources & evidence

ORD record
ord-b99fcf6a74c94e7fba1731c0e6160e37
Source dataset
uspto-grants-2008_10
Patent number
US07442693B2

Reaction notes

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