Water → HCID 86741806, compound

HRID 477689Notes

Reaction equation

HRID 477689 reaction equation
C([NH:3][C:4]1[CH:38]=[CH:37][CH:36]=[CH:35][C:5]=1[C:6]([NH:8][CH2:9]CN1CCC(NC2N(CC3C=CC(F)=CC=3)C3C=CC=CC=3N=2)CC1)=[O:7])C.C(=O)([O-])[O-:40].[Na+].[Na+].C([Cl:49])(=O)OC.O>ClCCl>[ClH:49].[ClH:49].[NH:3]1[C:4]2[C:5](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:6](=[O:7])[NH:8][C:9]1=[O:40]

Participants

6

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 10340Sodium CarbonateHCID 13983255HCID 13983255, compound

Product 1

HCID 86741806HCID 86741806, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of 4 parts of 2-(ethylamino)-N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]benzamide, 1.06 parts of sodium carbonate and 65 parts of dichloromethane was added dropwise a solution of 2 parts of methyl carbonochloridate in dichloromethane. Upon completion, stirring was continued overnight at reflux temperature. Water was added and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in acetonitrile and 2-propanol. The salt was filtered off and dried, yielding 1.8 parts of 1-ethyl-3-[2-[4-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-2,4(1H,3H)-quinazolinedione dihydrochloride; mp. +260° C. (compound 125).

Workup

  1. temperatureat reflux temperature
  2. extractionthe product was extracted with dichloromethane
  3. customThe extract was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. filtrationThe salt was filtered off
  11. customdried

Sources & evidence

ORD record
ord-b5977b8272cc42c3beb8b140d232550a
Source dataset
uspto-grants-1989_12
Patent number
US04888426

Reaction notes

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