1,1'-Carbonyldiimidazole → HCID 67388011, compound

HRID 905543Notes

Reaction equation

HRID 905543 reaction equation
[Br:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[O:14][CH:15]1[CH2:32][CH:31]2[N:17]([C:18](=[O:38])[N:19]([CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH:26]3[C:28]([C:34](O)=[O:35])([NH:29][C:30]2=[O:33])[CH2:27]3)[CH2:16]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:51]1([S:54]([NH2:57])(=[O:56])=[O:55])[CH2:53][CH2:52]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[Br:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[O:14][CH:15]1[CH2:32][CH:31]2[N:17]([C:18](=[O:38])[N:19]([CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH:26]3[C:28]([C:34]([NH:57][S:54]([CH:51]4[CH2:53][CH2:52]4)(=[O:56])=[O:55])=[O:35])([NH:29][C:30]2=[O:33])[CH2:27]3)[CH2:16]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 67387766HCID 67387766, compound

Product 1

HCID 67388011HCID 67388011, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 50 (151 mg, 0.257 mmol) and carbonyldiimidazole (162 mg, 0.437 mmol) in dry THF (10 mL) was stirred at reflux under nitrogen for 2 h. Optionally, the azalactone derivative, if desired, can be isolated. Then, the reaction mixture was cooled to room temperature and cyclopropylsulfonamide (58 mg, 0.482 mmol) and DBU (76 mg, 0.502 mmol) were added. The resulting solution was stirred at 50° C. for 12 h, then cooled to room temperature. The reaction mixture was quenched with water and extracted with AcOEtethyl acetate, dried (MgSO4), filtered and evaporated. The crude material was purified by column chromatography (CH2Cl2/EtOAc, 95:5). The solid obtained was triturated in water, filtered, dried under high vacuum, triturated in diethylether and dried again under high vacuum to give 138 mg (77%) of the title product 51 as a white powder: m/z=691 (M+H)+; 1H-NMR (CDCl3): 10.70 (br s, 1H), 8.12 (d, J=9.1 Hz, 1H), 7.97 (d, J=6.3 Hz, 1H), 7.54 (d, J=6.3 Hz, 1H), 7.21 (d, J=9.1 Hz, 1H), 6.70 (bs, 1H), 5.88 (bs, 1H), 5.74 (dd, J=17.3 Hz, 8.3 Hz, 1H), 5.16 (t, J=10.4 Hz, 1H), 4.74 (dd, J=9.4 Hz, 7.3 Hz, 1H), 4.11-3.98 (m, 4H), 3.69-3.55 (m, 2H), 3.27-3.10 (m, 1H), 3.02-2.89 (m, 1H), 2.83 (s, 3H), 2.58-2.35 (m, 3H), 2.29-2.13 (m, 1H), 2.11-1.92 (m, 2H), 1.75-0.76 (m, 9H).

Workup

  1. temperatureat reflux under nitrogen for 2 h
  2. customcan be isolated
  3. temperaturecooled to room temperature
  4. customThe reaction mixture was quenched with water
  5. extractionextracted with AcOEtethyl acetate
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude material was purified by column chromatography (CH2Cl2/EtOAc, 95:5)
  10. customThe solid obtained
  11. customwas triturated in water
  12. filtrationfiltered
  13. customdried under high vacuum
  14. customtriturated in diethylether
  15. customdried again under high vacuum

Sources & evidence

ORD record
ord-2b766884f590462b91db50bc405f6a8d
Source dataset
uspto-grants-2011_09
Patent number
US08012939B2

Reaction notes

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