Trifluoroacetic acid → HCID 45377100, compound

HRID 2047355Notes

Reaction equation

HRID 2047355 reaction equation
[Cl:1][C:2]1[C:6]([C:7]2[N:11]([CH3:12])[N:10]=[CH:9][CH:8]=2)=[C:5]([Cl:13])[S:4][C:3]=1[NH:14][C:15](=[O:32])[CH:16]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:17][NH:18]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[NH2:18][CH2:17][CH:16]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:15]([NH:14][C:3]1[S:4][C:5]([Cl:13])=[C:6]([C:7]2[N:11]([CH3:12])[N:10]=[CH:9][CH:8]=2)[C:2]=1[Cl:1])=[O:32]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58388245HCID 58388245, compound

Product 1

HCID 45377100HCID 45377100, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl (3-{[3,5-dichloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thienyl]amino}-3-oxo-2-phenylpropyl)carbamate (320 mg, 0.646 mmol) in dichloromethane (6.459 ml) at 25° C. was added TFA (0.498 ml, 6.46 mmol). After 30 min, the solution was dry loaded onto silica and neutralized through silica (0-20% MeOH in DCM (1% NH4OH) affording the free base of the title compound. The free base was then dissolved in MeOH (10 mL) and treated with excess 4M HCl in dioxane (2 mL) providing the HCl salt of 3-amino-N-[3,5-dichloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thienyl]-2-phenylpropanamide (188 mg, 0.414 mmol, 64.0% yield) as an orange solid: LCMS (ES) m/e 395, 397 (M, M+2)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 11.65 (s, 1 H) 8.18 (br. s., 3 H) 7.55 (d, J=1.77 Hz, 1 H) 7.28-7.51 (m, 1 H) 7.41 (d, J=5.05 Hz, 4 H) 6.36 (d, J=6.06 Hz, 1 H) 4.53 (dd, J=9.09, 5.31 Hz, 1 H) 3.81 (br. s., 3 H) 3.48-3.59 (m, 1 H) 3.01-3.17 (m, 1 H).

Workup

  1. customthe solution was dry

Sources & evidence

ORD record
ord-70e7fa72537e4107b3c0aff11512ee66
Source dataset
uspto-grants-2013_11
Patent number
US08592475B2

Reaction notes

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