Trifluoroacetic acid → Benzamide

HRID 2367744Notes

Reaction equation

HRID 2367744 reaction equation
S1C=C(C2C=CC(C(O)=O)=CC=2)N=N1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.NC[C:30]1[CH:31]=[C:32]([CH:52]=[CH:53][CH:54]=1)[C:33]([NH:35]C1SC2C[C@@H](NC(=O)C(F)(F)F)CCC=2N=1)=[O:34].CCN(CC)CC.FC(F)(F)C(N)=O.C(=O)([O-])[O-].[K+].[K+].C(O)(C(F)(F)F)=O>CN(C=O)C.CO.O>[C:33]([NH2:35])(=[O:34])[C:32]1[CH:52]=[CH:53][CH:54]=[CH:30][CH:31]=1

Participants

10

Reactant 7

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 67717TrifluoroacetamideHCID 682631,1'-CarbonyldiimidazoleHCID 27764514-(1,2,3-Thiadiazol-4-yl)benzoic acidHCID 86667237HCID 86667237, compound

Product 1

HCID 2331BenzamideYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

Stir a solution of 4-[1,2,3]thiadiazol-4-yl-benzoic acid (21 mg, 0.10 mmol) and CDI (19 mg, 0.11 mmol) in DMF (3 mL) at rt for 1.5 h. To the clear solution add 3-aminomethyl-N—[(S)-6-(2,2,2-trifluoro-acetylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide hydrochloride (45 mg, 0.10 mmol) followed by Et3N (0.098 mL, 0.70 mmol). Stir the mixture at rt overnight. Concentrate and use the mixture in the next step without any purification. Dissolve the crude trifluoroacetamide (50 mg, 0.085 mmol) in 4:1 MeOH/H2O (10 mL). Add potassium carbonate (47 mg, 0.34 mmol) to the mixture and stir at 50° C. for 48 h. Add a small amount of TFA to the mixture and purify by prep-HPLC (10% to 100%, CH3CN/H2O) to give the desired product N—((S)-6-amino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-3-(4-[1,2,3]thiadiazol-4-yl)-aminomethyl)-benzamide in 48% yield (20 mg, 0.041 mmol) MS, electrospray 491.1 (M+H), rt 0.55 min.

Workup

  1. concentrationConcentrate
  2. customuse the mixture in the next step without any purification
  3. custompurify by prep-HPLC (10% to 100%, CH3CN/H2O)

Sources & evidence

ORD record
ord-89ab6d4bec744199b5d4a66b617db814
Source dataset
uspto-grants-2014_04
Patent number
US08697911B2

Reaction notes

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