Sodium hydride → HCID 69021140, compound

HRID 860819Notes

Reaction equation

HRID 860819 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:10]2[C:16]3[CH:17]=[C:18]([C:21]([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=4)([OH:28])[C:22]4[N:26]([CH3:27])[CH:25]=[N:24][CH:23]=4)[CH:19]=[CH:20][C:15]=3[NH:14][C:13](=[O:36])[CH2:12][S:11]2)[CH:7]=[CH:8][CH:9]=1.Br[CH2:38][CH:39]1[CH2:41][CH2:40]1>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([CH:10]2[C:16]3[CH:17]=[C:18]([C:21]([C:29]4[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=4)([OH:28])[C:22]4[N:26]([CH3:27])[CH:25]=[N:24][CH:23]=4)[CH:19]=[CH:20][C:15]=3[N:14]([CH2:38][CH:39]3[CH2:41][CH2:40]3)[C:13](=[O:36])[CH2:12][S:11]2)[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 10118352HCID 10118352, compound

Product 1

HCID 69021140HCID 69021140, compoundYield 17.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (0.0016 mol, 60% in oil) was added portionwise at 10° C. to a mixture of 5-(3-chlorophenyl)-7-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (0.0013 mol), obtained in Example B2, in DMF (7 ml). The mixture was stirred for 30 minutes. (Bromomethyl)-cyclopropane (0.0016 mol) was added. The mixture was brought to room temperature, then stirred for 3 hours, poured out into ice water and stirred again for 30 minutes. The precipitate was filtered and taken up in DCM. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (0.6 g) was purified by column chromatography over kromasil (eluent: CH2Cl2/CH3OH/NEt3 97/3/0.1; 10 μm). The pure fractions were collected and the solvent was evaporated. The residue (0.16 g) was crystallized from acetonitrile. The precipitate was filtered off and dried, yielding 0.13 g (17%) of 5-(3-chlorophenyl)-7-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-(cyclopropylmethyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one, mp. 245° C.

Workup

  1. customwas brought to room temperature
  2. stirringstirred for 3 hours
  3. stirringstirred again for 30 minutes
  4. filtrationThe precipitate was filtered
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue (0.6 g) was purified by column chromatography over kromasil (eluent: CH2Cl2/CH3OH/NEt3 97/3/0.1; 10 μm)
  10. customThe pure fractions were collected
  11. customthe solvent was evaporated
  12. customThe residue (0.16 g) was crystallized from acetonitrile
  13. filtrationThe precipitate was filtered off
  14. customdried

Sources & evidence

ORD record
ord-4081494c04aa43f284aec6cee3c09eea
Source dataset
uspto-grants-2006_12
Patent number
US07153958B2

Reaction notes

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