Tetrahydrofuran → HCID 13983228, compound

HRID 1493938Notes

Reaction equation

HRID 1493938 reaction equation
[CH2:1]([NH:3][C:4]1[CH:38]=[CH:37][CH:36]=[CH:35][C:5]=1[C:6]([NH:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([NH:17][C:18]2[N:22]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[C:21]3[CH:31]=[CH:32][CH:33]=[CH:34][C:20]=3[N:19]=2)[CH2:13][CH2:12]1)=[O:7])[CH3:2].C(N(CC)CC)C.[C:46](Cl)(=[O:50])[O:47][CH2:48][CH3:49].[O:52]1CCC[CH2:53]1>>[CH2:1]([N:3]1[C:4]2[C:5](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:6](=[O:7])[N:8]([CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH:14]([N:17]([C:18]3[N:22]([CH2:23][C:24]4[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=4)[C:21]4[CH:31]=[CH:32][CH:33]=[CH:34][C:20]=4[N:19]=3)[C:46](=[O:50])[O:47][CH2:48][CH3:49])[CH2:15][CH2:16]2)[C:53]1=[O:52])[CH3:2]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 13983255HCID 13983255, compound

Product 1

HCID 13983228HCID 13983228, compoundYield 25%

Procedure

To a stirred mixture of 7.7 parts of 2-(ethylamino)-N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]-ethyl]benzamide, 2 parts of N,N-diethylethanamine and 90 parts of tetrahydrofuran were added dropwise 1.6 parts of ethyl carbonochloridate. Upon completion, stirring was continued for 1 hour at room temperature. The reaction mixture was evaporated and 4-methyl-2-pentanone was added to the residue. The organic phase was washed with water, 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 further purified by HPLC using a mixture of methylbenzene and ethanol (90:10 by volume) as eluent. The pure fraction was collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 2.2 parts (25%) of ethyl [1-[2-[1-ethyl-1,4-dihydro-2,4-dioxo-3(2H)-quinazolinyl]ethyl]-4-piperidinyl]-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbamate; mp. 160.3° C. (compound 124).

Workup

  1. customThe reaction mixture was evaporated
  2. addition4-methyl-2-pentanone was added to the residue
  3. washThe organic phase was washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was further purified by HPLC
  12. additiona mixture of methylbenzene and ethanol (90:10 by volume) as eluent
  13. customThe pure fraction was collected
  14. customthe eluent was evaporated
  15. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-0f3daed358904fdb9c271d232d2e2cd6
Source dataset
uspto-grants-1991_06
Patent number
US05025014

Reaction notes

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