Diisopropylcarbodiimide → methyl 1-{3-[(tert-butoxycarbonyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-6-carboxylate

HRID 1784300

Reaction equation

HRID 1784300 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:13]=[C:14]=S)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C(N=C=NC(C)C)(C)C.[NH2:25][C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][C:27]=1[NH:36][CH2:37][CH2:38][CH2:39][NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>O1CCCC1>[C:44]([O:43][C:41]([NH:40][CH2:39][CH2:38][CH2:37][N:36]1[C:27]2[CH:28]=[C:29]([C:30]([O:32][CH3:33])=[O:31])[CH:34]=[CH:35][C:26]=2[N:25]=[C:14]1[NH:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=1)=[O:42])([CH3:46])([CH3:47])[CH3:45]

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 1189003,4,5-Trimethoxyphenyl isothiocyanateHCID 11962077Methyl 4-amino-3-({3-[(tert-butoxycarbonyl)amino]propyl}amino)benzoate

Product 1

HCID 11962078methyl 1-{3-[(tert-butoxycarbonyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-6-carboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3,4,5-trimethoxyphenyl isothiocyanate (6.6 g, 1.2 eq) and diisopropylcarbodiimide (9.1 g, 3 eq) are successively added to a solution of methyl 4-amino-3-({3-[(tert-butoxycarbonyl)amino]propyl}amino)benzoate (7.75 g, 1 eq) in tetrahydrofuran (130 ml). The mixture is heated under reflux for 16 hours then cooled down to ambient temperature and concentrated under reduced pressure at 40° C. Water (100 ml) and dichloromethane (200 ml) are added to the residue obtained. After decantation and extractions, the combined organic phases are washed with salt water, dried over Na2SO4 then concentrated under reduced pressure at 40° C. Purification of the residue by flash chromatography on silica gel (eluent:heptane/ethyl acetate 8:2 to 3:7) produces the expected compound in the form of a solid which is washed with ether. (4.4 g; 36% yield).

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 16 hours
  3. concentrationconcentrated under reduced pressure at 40° C
  4. additionWater (100 ml) and dichloromethane (200 ml) are added to the residue
  5. customobtained
  6. extractionAfter decantation and extractions
  7. washthe combined organic phases are washed with salt water
  8. dry with materialdried over Na2SO4
  9. concentrationthen concentrated under reduced pressure at 40° C
  10. customPurification of the residue by flash chromatography on silica gel (eluent:heptane/ethyl acetate 8:2 to 3:7)

Sources & evidence

ORD record
ord-42067fc6e84247f4918deb5357125a06
Source dataset
uspto-grants-2009_03
Patent number
US07501525B2

Linked notes

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