1,1'-Carbonyldiimidazole → HCID 67387571, compound

HRID 905541Notes

Reaction equation

HRID 905541 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]([C:9]3[N:10]=[C:11]([O:21][CH:22]4[CH2:39][CH:38]5[CH:24]([C:25](=[O:45])[N:26]([CH3:44])[CH2:27][CH2:28][CH2:29][CH2:30][CH:31]=[CH:32][CH:33]6[C:35]([C:41](O)=[O:42])([NH:36][C:37]5=[O:40])[CH2:34]6)[CH2:23]4)[C:12]4[C:17]([CH:18]=3)=[CH:16][C:15]([O:19][CH3:20])=[CH:14][CH:13]=4)[S:7][CH:8]=2)[CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:58]1([S:61]([NH2:64])(=[O:63])=[O:62])[CH2:60][CH2:59]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[CH:1]1([C:4]2[N:5]=[C:6]([C:9]3[N:10]=[C:11]([O:21][CH:22]4[CH2:39][CH:38]5[CH:24]([C:25](=[O:45])[N:26]([CH3:44])[CH2:27][CH2:28][CH2:29][CH2:30][CH:31]=[CH:32][CH:33]6[C:35]([C:41]([NH:64][S:61]([CH:58]7[CH2:60][CH2:59]7)(=[O:63])=[O:62])=[O:42])([NH:36][C:37]5=[O:40])[CH2:34]6)[CH2:23]4)[C:12]4[C:17]([CH:18]=3)=[CH:16][C:15]([O:19][CH3:20])=[CH:14][CH:13]=4)[S:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418Cyclopropanesulfonamide2×HCID 67387700HCID 67387700, compound

Product 1

HCID 67387571HCID 67387571, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 29 (91 mg, 0.14 mmol) and 1,1′-carbonyldiimidazole (CDI) (47 mg, 0.29 mmol) in dry THF (7 mL) was heated at reflux for 2 h under nitrogen. LCMS analysis shows one peak of the intermediate (RT=5.37). Optionally, the azalactone derivative, if desired, can be isolated. The reaction mixture was cooled to room temperature and cyclopropylsulfonamide (52 mg, 0.43 mmol) was added. Then, DBU (50 μL, 0.33 mmol) was added and the reaction mixture was stirred at room temperature for 1 h, and then heated at 55° C. for 24 h. The solvent was evaporated, and the residue partitioned between AcOEt ethyl acetate and acidic water (pH=3). The crude material was purified by column chromatography (ethyl acetateAcOEt/CH2Cl2/pPetroleum ether, 1:1:1). The residue was crystallized in diethyl ether, filtered to give the target compound contaminated with the cyclopropylsulfonamide. This material was triturated in 3 mL of water, filtered, washed with water and dried overnight with the high vacuum pump to give 60 mg (57%) of the target compound 30 as a slightly yellow powder: m/z=734 (M+H)+, 1H-NMR (CDCl3): 10.94 (s, 1H), 8.08 (d, J=8.6 Hz, 1H), 8.00 (s, 1H), 7.12-7.15 (m, 2H), 6.91 (s, 1H), 6.35 (s, 1H), 5.74-5.77 (m, 1H), 5.63-5.69 (m, 1H), 5.06 (t, J=10.4 Hz, 1H), 4.60 (t, J=12.3 Hz, 1H), 3.93 (s, 3H), 3.35-3.42 (m, 2H), 3.04 (s, 3H), 2.89-2.96 (m, 2H), 2.52-2.52 (m, 2H), 2.37-2.45 (m, 2H), 2.10-2.32 (m, 2H), 1.61-1.93 (m, 4H), 1.3-1.51 (m, 4H), 0.90-1.30 (m, 8H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h under nitrogen
  3. customone peak of the intermediate (RT=5.37)
  4. customcan be isolated
  5. temperatureheated at 55° C. for 24 h
  6. customThe solvent was evaporated
  7. customthe residue partitioned between AcOEt ethyl acetate and acidic water (pH=3)
  8. customThe crude material was purified by column chromatography (ethyl acetateAcOEt/CH2Cl2/pPetroleum ether, 1:1:1)
  9. customThe residue was crystallized in diethyl ether
  10. filtrationfiltered
  11. customto give the target compound
  12. customThis material was triturated in 3 mL of water
  13. filtrationfiltered
  14. washwashed with water
  15. customdried overnight with the high vacuum pump

Sources & evidence

ORD record
ord-f36be9597caa4ecda1ae13734173d8ec
Source dataset
uspto-grants-2011_09
Patent number
US08012939B2

Reaction notes

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