Cesium carbonate → Diethyl 2-(4-tert-butoxycarbonylaminobutyl)-2-[1-(5-cyclopropyl-[1,3,4]thiadiazol-2-ylmethyl)-1H-imidazol-4-yl]malonate

HRID 1666986Notes

Reaction equation

HRID 1666986 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:8][C:9]1[S:10][C:11]([CH:14]2[CH2:16][CH2:15]2)=[N:12][N:13]=1.[C:17]([O:21][C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([C:40]1[N:41]=[CH:42][NH:43][CH:44]=1)([C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:23])([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[C:17]([O:21][C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([C:40]1[N:41]=[CH:42][N:43]([CH2:8][C:9]2[S:10][C:11]([CH:14]3[CH2:16][CH2:15]3)=[N:12][N:13]=2)[CH:44]=1)([C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:23])([CH3:19])([CH3:20])[CH3:18]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27576792-(Chloromethyl)-5-cyclopropyl-1,3,4-thiadiazoleHCID 178471441HCID 178471441, compound

Product 1

HCID 67443151Diethyl 2-(4-tert-butoxycarbonylaminobutyl)-2-[1-(5-cyclopropyl-[1,3,4]thiadiazol-2-ylmethyl)-1H-imidazol-4-yl]malonateYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Together with 1.97 g (6.04 mmol) of cesium carbonate and 0.29 g (1.66 mmol) of 2-chloromethyl-5-cyclopropyl-1,3,4-thiadiazole, a solution of 0.60 g (1.51 mmol) of diethyl 2-(4-tert-butoxycarbonylaminobutyl)-2-(1H-imidazol-4-yl)malonate in 12 ml of DMF was heated at 75° C. for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was taken up in ethyl acetate and washed with water. The organic phase was dried over Na2SO4, filtered and concentrated. Chromatographic purification of the residue on silica gel (CH2Cl2:MeOH:water:acetic acid 95:5:0.5:0.5) gave 0.145 g (18%) of the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washwashed with water
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customChromatographic purification of the residue on silica gel (CH2Cl2:MeOH:water:acetic acid 95:5:0.5:0.5)

Sources & evidence

ORD record
ord-264ef64331ce40d6b8eaf08f6d8f4d28
Source dataset
uspto-grants-2011_10
Patent number
US08044208B2

Reaction notes

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