Tetrahydrofuran → HCID 13588096, compound

HRID 637419Notes

Reaction equation

HRID 637419 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11]2[N:15]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:14]3[CH:24]=[CH:25][CH:26]=[CH:27][C:13]=3[N:12]=2)[CH2:6][CH2:5]1.C(N(CC)CC)C.[Cl:35][C:36]1[N:41]=[C:40](Cl)[CH:39]=[CH:38][N:37]=1.[O:43]1CCCC1>>[OH2:43].[ClH:35].[ClH:35].[Cl:35][C:36]1[N:41]=[C:40]([NH:1][CH2:2][CH2:3][N:4]2[CH2:9][CH2:8][CH:7]([NH:10][C:11]3[N:15]([CH2:16][C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=4)[C:14]4[CH:24]=[CH:25][CH:26]=[CH:27][C:13]=4[N:12]=3)[CH2:6][CH2:5]2)[CH:39]=[CH:38][N:37]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 775312,4-DichloropyrimidineHCID 12891741N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine

Product 1

HCID 13588096HCID 13588096, compound

Conditions

Temperature
-20 °C

Procedure

A mixture of 3.7 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine, 1 part of N,N-diethylethanamine and 45 parts of tetrahydrofuran was stirred at -20° C. and there was added dropwise a solution of 1.5 parts of 2,4-dichloropyrimidine in tetrahydrofuran at this temperature. Upon completion, the mixture was allowed to reach slowly room temperature and stirring was continued overnight at room temperature. The precipitate was filtered off and the filtrate was evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume), saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanol. The salt was filtered off and dried, yielding 1.7 parts of N-[1-[2-[(2-chloro-4-pyrimidinyl)amino]ethyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]1H-benzimidazol-2-amine dihydrochloride monohydrate; mp. 287.4° C. (compound 60).

Workup

  1. customto reach slowly room temperature
  2. stirringstirring
  3. filtrationThe precipitate was filtered off
  4. customthe filtrate was evaporated
  5. customThe residue was purified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol (90:10 by volume)
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. filtrationThe salt was filtered off
  10. customdried

Sources & evidence

ORD record
ord-613189517f7d4b01af80f58ac790769b
Source dataset
uspto-grants-1985_12
Patent number
US04556660

Reaction notes

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