Hydrochloric Acid → 1-[2-(4-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]-3-[4-(trifluoromethyl)phenyl]urea hydrochloride

HRID 412350Notes

Reaction equation

HRID 412350 reaction equation
[ClH:1].Cl.[NH2:3][CH2:4][CH2:5][C:6]1[CH:38]=[CH:37][C:9]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[N:18]=[C:17]([CH2:19][O:20][C:21]4[CH:34]=[CH:33][C:24]([CH2:25][CH:26]5[S:30][C:29](=[O:31])[NH:28][C:27]5=[O:32])=[CH:23][CH:22]=4)[N:16]([CH3:35])[C:15]=3[CH:36]=2)=[CH:8][CH:7]=1.[F:39][C:40]([F:51])([F:50])[C:41]1[CH:46]=[CH:45][C:44]([N:47]=[C:48]=[O:49])=[CH:43][CH:42]=1.C(N(CC)CC)C.Cl>O1CCCC1.O1CCOCC1.C(OCC)C.CN(C)C=O>[ClH:1].[O:31]=[C:29]1[NH:28][C:27](=[O:32])[CH:26]([CH2:25][C:24]2[CH:33]=[CH:34][C:21]([O:20][CH2:19][C:17]3[N:16]([CH3:35])[C:15]4[CH:36]=[C:11]([O:10][C:9]5[CH:8]=[CH:7][C:6]([CH2:5][CH2:4][NH:3][C:48]([NH:47][C:44]6[CH:43]=[CH:42][C:41]([C:40]([F:39])([F:50])[F:51])=[CH:46][CH:45]=6)=[O:49])=[CH:38][CH:37]=5)[CH:12]=[CH:13][C:14]=4[N:18]=3)=[CH:22][CH:23]=2)[S:30]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 865877735-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 185375661-[2-(4-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]-3-[4-(trifluoromethyl)phenyl]urea hydrochlorideYield 79.7%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

1-[2-(4-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]-3-(4-trifluoromethylphenyl)urea hydrochloride was obtained by a similar procedure to that described in Example 31 using 5-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (0.3 g), α,α,α-trifluoro-p-tolyl isocyanate (97 mg), triethylamine (65 mg) and anhydrous N,N-dimethylformamide (5 ml). To a solution of the product in tetrahydrofuran (10 ml) was added 4N hydrogen chloride in 1,4-dioxane (10 ml) and the mixture was stirred at room temperature for 3 hours. To the reaction mixture was added diethyl ether (50 ml) and this mixture was further stirred for 30 minutes. The precipitate was isolated by filtration and washed with ethyl acetate to afford the title compound (0.3 g, mp 153-156° C.).

Workup

  1. stirringthis mixture was further stirred for 30 minutes
  2. customThe precipitate was isolated by filtration
  3. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-3523880492f942cda65b0e750a510951
Source dataset
uspto-grants-2003_05
Patent number
US06562849B1

Reaction notes

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