Triethylamine → 5-[4-[6-(4-n-Hexylaminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4dione

HRID 2303824Notes

Reaction equation

HRID 2303824 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12](C(OC(C)(C)C)=O)=[CH:11][C:10]=2NCCCCCC)=[CH:4][C:3]=1[N:29]([CH3:37])[C:30](=O)OC(C)(C)C.[O:38]=[C:39]1[NH:43][C:42](=[O:44])[CH:41]([CH2:45][C:46]2[CH:56]=[CH:55][C:49]([O:50][CH2:51]C(O)=O)=[CH:48][CH:47]=2)[S:40]1.C([N:59]([CH2:62][CH3:63])CC)C>O1CCCC1>[CH2:62]([NH:59][C:12]1[CH:11]=[CH:10][C:9]([O:8][C:5]2[CH:6]=[CH:7][C:2]3[N:1]=[C:37]([CH2:51][O:50][C:49]4[CH:48]=[CH:47][C:46]([CH2:45][CH:41]5[S:40][C:39](=[O:38])[NH:43][C:42]5=[O:44])=[CH:56][CH:55]=4)[N:29]([CH3:30])[C:3]=3[CH:4]=2)=[CH:14][CH:13]=1)[CH2:63][CH2:7][CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 113234852-(4-((2,4-Dioxothiazolidin-5-YL)methyl)phenoxy)acetic acidHCID 68565430t-butyl N-[2-amino-5-(4-t-butoxycarbonyl-n-hexylaminophenoxy)phenyl]-N-methylcarbamate

Product 1

HCID 865877705-[4-[6-(4-n-Hexylaminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4dioneYield 129.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of t-butyl N-[2-amino-5-(4-t-butoxycarbonyl-n-hexylaminophenoxy)phenyl]-N-methylcarbamate (4.10 g), 4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxyacetic acid (2.81 g), diethyl cyanophsphonate (1.63 g), triethylamine (1.01 g) and anhydrous tetrahydrofuran (100 ml) was stirred at ambient temperature for 28 hours. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated. A mixture of the residue and 4N hydrogen chloride/dioxane (50 ml) was stirred at ambient temperature for 66 hours. Water was added to the reaction mixture and the mixture was neutralized with sodium bicarbonate and extracted with ethyl acetate. The ethyl acetate was dried over anhydrous sodium sulfate and evaporated. The residue was purified by chromatography on a silica gel column using n-hexane/ethyl acetate=2/3 as the eluant to give the title compound (2.89 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and water
  3. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. additionA mixture of the residue and 4N hydrogen chloride/dioxane (50 ml)
  6. stirringwas stirred at ambient temperature for 66 hours
  7. additionWater was added to the reaction mixture
  8. extractionextracted with ethyl acetate
  9. dry with materialThe ethyl acetate was dried over anhydrous sodium sulfate
  10. customevaporated
  11. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-395ee05524324ed68adb82eae0253774
Source dataset
uspto-grants-2002_08
Patent number
US06432993B1

Reaction notes

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