Trifluoroacetic acid → HCID 45377097, compound

HRID 2047358Notes

Reaction equation

HRID 2047358 reaction equation
CC([N:5]([CH2:9][CH:10]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:11]([NH:13][C:14]1[S:15][C:16]([Cl:26])=[C:17]([C:19]2[N:23]([CH3:24])[N:22]=[CH:21][C:20]=2[Cl:25])[CH:18]=1)=[O:12])C(=O)[O-])(C)C.C(O)(C(F)(F)F)=O>ClCCl>[NH2:5][CH2:9][CH:10]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:11]([NH:13][C:14]1[S:15][C:16]([Cl:26])=[C:17]([C:19]2[N:23]([CH3:24])[N:22]=[CH:21][C:20]=2[Cl:25])[CH:18]=1)=[O:12]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86656476HCID 86656476, compound

Product 1

HCID 45377097HCID 45377097, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl[3-{[5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thienyl]amino}-3-oxo-2-(phenylmethyl)propyl]carbamate (740 mg, 1.453 mmol) in dichloromethane (7.263 ml) at 25° C. was added TFA (1.119 ml, 14.53 mmol) in one portion. 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-[5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thienyl]-2-(phenylmethyl)propanamide (426 mg, 0.908 mmol, 62.5% yield) as an orange solid: LCMS (ES) m/e 409, 411 (M, M+2)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (s, 1 H) 8.06 (br. s., 3 H) 7.68 (s, 1 H) 7.26-7.40 (m, 4 H) 7.24 (d, J=6.82 Hz, 1 H) 6.70 (s, 1 H) 3.94-3.96 (m, 1 H) 3.70 (s, 3 H) 3.14-3.17 (m, 1 H) 3.05 (dd, J=13.52, 6.44 Hz, 2 H) 2.85 (dd, J=14.02, 7.45 Hz, 2 H).

Workup

  1. customthe solution was dry

Sources & evidence

ORD record
ord-1fcc2e58a527433caabcc5ab102cf3d7
Source dataset
uspto-grants-2013_11
Patent number
US08592475B2

Reaction notes

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