Hydrochloric Acid → 4-(3-Chloro-phenyl)-2-[6-(4-methyl-piperazine-1-carbonyl)-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide

HRID 1667700Notes

Reaction equation

HRID 1667700 reaction equation
[C:1]([C:4]1[S:8][C:7]([N:9]2[C:13]3[CH:14]=[C:15]([C:18]([OH:20])=O)[CH:16]=[CH:17][C:12]=3[N:11]=[CH:10]2)=[N:6][C:5]=1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=1)(=[O:3])[NH2:2].[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)N=N1)C.F[P-](F)(F)(F)(F)F.Cl>O.CN(C)C=O>[Cl:27][C:23]1[CH:22]=[C:21]([C:5]2[N:6]=[C:7]([N:9]3[C:13]4[CH:14]=[C:15]([C:18]([N:32]5[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]5)=[O:20])[CH:16]=[CH:17][C:12]=4[N:11]=[CH:10]3)[S:8][C:4]=2[C:1]([NH2:2])=[O:3])[CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9886HexafluorophosphateHCID 531671-MethylpiperazineHCID 674273413-[5-carbamoyl-4-(3-chloro-phenyl)-thiazol-2-yl]-3H-benzoimidazole-5-carboxylic acidHCID 178484285HCID 178484285, compound

Product 1

HCID 468305804-(3-Chloro-phenyl)-2-[6-(4-methyl-piperazine-1-carbonyl)-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.05 g (0.15 mmole) of 3-[5-Carbamoyl-4-(3-chloro-phenyl)-thiazol-2-yl]-3H-benzoimidazole-5-carboxylic acid (I.10a), 0.050 mL of N-methyl-piperazine, 0.070 g (0.18 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium, 3-oxide, hexafluorophosphate(1-) (1:1) and 4 mL of dimethylformamide was stirred at room temperature for 16 hours. The mixture was poured into 50 mL of water and made acidic by addition of 1 M hydrochloric acid. The aqueous layer was extracted three times with 20 mL of ethyl acetate and then made basic by addition of potassium carbonate solution. The mixture was extracted three times with 20 ml, of ethyl acetate. The combined organic extracts were washed with 20 mL of water, 20 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with methanol-dichloromethane (7:93) to give 0.021 g of 4-(3-chloro-phenyl)-2-[6-(4-methyl-piperazine-1-carbonyl)-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.11) as a yellow solid. MH+/Z=481

Workup

  1. extractionThe aqueous layer was extracted three times with 20 mL of ethyl acetate
  2. additionmade basic by addition of potassium carbonate solution
  3. extractionThe mixture was extracted three times with 20 ml
  4. washThe combined organic extracts were washed with 20 mL of water, 20 mL of brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with methanol-dichloromethane (7:93)

Sources & evidence

ORD record
ord-f9517a37b16c402ba733dab8309abf22
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

Loading…