Ethyl orthoformate → 2-[6-(4-Methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-phenyl-thiazole-5-carboxylic acid ethyl ester

HRID 1667681Notes

Reaction equation

HRID 1667681 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:12]2[CH:17]=[C:16]([CH2:18][N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[CH:15]=[CH:14][C:13]=2[NH2:26])=[N:8][C:7]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:5])[CH3:2].[CH:33](OCC)(OCC)OCC>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([N:11]2[C:12]3[CH:17]=[C:16]([CH2:18][N:19]4[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]4)[CH:15]=[CH:14][C:13]=3[N:26]=[CH:33]2)=[N:8][C:7]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 866428072-[2-Amino-5-(4-methyl-piperazin-1-ylmethyl)-phenylamino]-4-phenyl-thiazole-5-carboxylic acid ethyl ester

Product 1

HCID 674282602-[6-(4-Methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-phenyl-thiazole-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a mixture of 2-[2-amino-5-(4-methyl-piperazin-1-ylmethyl)-phenylamino]-4-phenyl-thiazole-5-carboxylic acid ethyl ester (VII.1a) from previous step and 0.2 mL of acetic acid was added 0.2 mL of triethyl orthoformate. The reaction mixture was heated to 60 degrees for 1 hour, and then concentrated under reduced pressure. The residue was diluted with 10 mL of water and 2 mL of saturated sodium bicarbonate and then extracted three times with 5 mL of dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with methanol-dichloromethane (gradient 0:100-10:90) to give 0.041 g of 2-[6-(4-methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-phenyl-thiazole-5-carboxylic acid ethyl ester (I.1a) as a white solid.

Workup

  1. temperatureThe reaction mixture was heated to 60 degrees for 1 hour
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with 10 mL of water and 2 mL of saturated sodium bicarbonate
  4. extractionextracted three times with 5 mL of dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with methanol-dichloromethane (gradient 0:100-10:90)

Sources & evidence

ORD record
ord-eb7b0fdeedb8463aa2ffa26a0c6e7e71
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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