Imidazole → HCID 21243175, compound

HRID 621505Notes

Reaction equation

HRID 621505 reaction equation
Br[CH2:2][C:3]1([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=2[Cl:43])[O:7][CH:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([C:22]4[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([C:29]5[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=5)[CH:23]=4)[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][O:4]1.[NH:44]1[CH:48]=[CH:47][N:46]=[CH:45]1.[H-].[Na+]>CS(C)=O>[Cl:43][C:37]1[CH:38]=[C:39]([Cl:42])[CH:40]=[CH:41][C:36]=1[C:3]1([CH2:2][N:44]2[CH:48]=[CH:47][N:46]=[CH:45]2)[O:7][CH:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:17][CH2:18][N:19]([C:22]4[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([C:29]5[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=5)[CH:23]=4)[CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:5][O:4]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 21243176HCID 21243176, compound

Product 1

HCID 21243175HCID 21243175, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

6.21 g (9.1 mmol) of 2-bromomethyl-2-(2,4-dichlorophenyl)-4-[4-(4-(2-methyl-4-(4-tolyl)pyrimidin-6-yl)piperazin-1-yl)phenoxymethyl]-1,3-dioxolane (mixture of cis/trans diastereomers) were reacted with 1.244 g (18.3 mmol) of imidazole and 0.55 g (18.2 mmol) of an 80% strength sodium hydride/oil dispersion in 26 ml of absolute dimethyl sulfoxide as described in Example 8b. After stirring for 26 hours at 130° C., the dimethyl sulfoxide (DMSO) was removed by distillation in an oil-pump vacuum. The residue remaining was taken up in CH2Cl2 /water. After thorough mixing and subsequent separation of the phases, the aqueous solution was extracted three times with CH2Cl2. The combined CH2Cl2 extracts were evaporated in vacuo. The residue remaining (4.30 g) was chromatographed on a silica gel S/CH2Cl2 column (diamter 2.0 cm, height 20 cm) with elution using CH2Cl2 and CH2Cl2 /C2H5OH mixtures (0.5-3.0% by volume of C2H5OH). The fractions containing the diastereomer racemates (check using TLC) were combined and evaporated in vacuo. In this fashion, 3.12 g (=51% yield) of 2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-4-[4-(4-(2-methyl-4-(4-tolyl)pyrimidin-6-yl)piperazin-1-yl)phenoxymethyl]-1,3-dioxolane (mixture of cis/trans diastereomers) were obtained as a viscous oil;

Workup

  1. customthe dimethyl sulfoxide (DMSO) was removed by distillation in an oil-pump vacuum
  2. additionAfter thorough mixing
  3. customsubsequent separation of the phases
  4. extractionthe aqueous solution was extracted three times with CH2Cl2
  5. customThe combined CH2Cl2 extracts were evaporated in vacuo
  6. customwas chromatographed on a silica gel S/CH2Cl2 column (diamter 2.0 cm, height 20 cm) with elution
  7. additionThe fractions containing the diastereomer racemates (check using TLC)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-b0491c2c7b804bf79751f52c0aa20009
Source dataset
uspto-grants-1989_04
Patent number
US04824846

Reaction notes

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