Dimethyl Sulfoxide → HCID 68008463, compound

HRID 1429096Notes

Reaction equation

HRID 1429096 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]([NH:27][C:28]([C:30]2[CH:34]=[C:33]([CH3:35])[O:32][N:31]=2)=[O:29])[C:20](=[O:36])[N:19]2[CH2:37][C@H:38]([O:40][C:41]3[N:42]=[C:43]4[C:48](=[C:49]5[C:54]=3[CH:53]=[CH:52][CH:51]=[CH:50]5)[CH:47]=[CH:46][CH:45]=[CH:44]4)[CH2:39][C@H:18]2[C:17](=[O:55])[NH:16][C@:15]2([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:56][C@H:14]2[CH2:13]1.C(N(CC)CC)C>ClCCl>[CH3:35][C:33]1[O:32][N:31]=[C:30]([C:28]([NH:27][C@@H:21]2[C:20](=[O:36])[N:19]3[CH2:37][C@H:38]([O:40][C:41]4[N:42]=[C:43]5[C:48](=[C:49]6[C:54]=4[CH:53]=[CH:52][CH:51]=[CH:50]6)[CH:47]=[CH:46][CH:45]=[CH:44]5)[CH2:39][C@H:18]3[C:17](=[O:55])[NH:16][C@:15]3([C:57]([O:59][C:60]([CH3:62])([CH3:61])[CH3:63])=[O:58])[CH2:56][C@H:14]3[CH2:13][C:12](=[O:11])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:29])[CH:34]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68008411HCID 68008411, compound

Product 1

HCID 68008463HCID 68008463, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (0.017 ml, 0.198 mmol) in dichloromethane (0.6 ml) cooled to −60° C. was added DMSO (0.030 ml, 0.419 mmol) dropwise. The mixture was stirred for 15 min and added dropwise a solution of compound (2R,6S,13aS,14aR,16aS)-tert-butyl 12-hydroxy-6-(5-methylisoxazole-3-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)octadecahydrocyclo propa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (Example 18h, 80 mg, 0.11 mmol) in dichloromethane (0.4 ml). The reaction mixture was stirred for 20 min at −60° C., and triethylamine (0.123 ml, 0.882 mmol) was added dropwise. The mixture was stirred at −60° C. for 5 min, and allowed to warm to room temperature with stirring for 10 min. The reaction mixture was quenched with water, stirred for 15 min, and diluted with dichloromethane. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to give a foamy material. The crude product was purified by flash chromatography on silica gel (5% methanol/dichloromethane) to provide the title compound (2R,6S,13aS,14aR,16aS)-tert-butyl 6-(5-methylisoxazole-3-carboxamido)-5, 12, 16-trioxo-2-(phenanthridin-6-yloxy)octadecahydrocyclopropa[e]pyrrolo [1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (47 mg, 59% yield) .

Workup

  1. stirringThe reaction mixture was stirred for 20 min at −60° C.
  2. stirringThe mixture was stirred at −60° C. for 5 min
  3. stirringwith stirring for 10 min
  4. customThe reaction mixture was quenched with water
  5. stirringstirred for 15 min
  6. additiondiluted with dichloromethane
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customto give a foamy material
  12. customThe crude product was purified by flash chromatography on silica gel (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-11df8c5ed1384ac5a4699f71c8768d0f
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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