Trifluoroacetic acid → 2-(3-(2-fluorobenzoyl)thioureido)-5,5-dimethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylic acid

HRID 2207772Notes

Reaction equation

HRID 2207772 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[C:4]([NH:6][C:7](=[S:27])[NH:8][C:9]1[S:19][C:12]2[CH2:13][O:14][C:15]([CH3:18])([CH3:17])[CH2:16][C:11]=2[C:10]=1[C:20]([O:22]C(C)(C)C)=[O:21])=[O:5].FC(F)(F)C(O)=O>C(Cl)Cl>[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[C:4]([NH:6][C:7](=[S:27])[NH:8][C:9]1[S:19][C:12]2[CH2:13][O:14][C:15]([CH3:17])([CH3:18])[CH2:16][C:11]=2[C:10]=1[C:20]([OH:22])=[O:21])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86731959tert-butyl 2-(3-(2-fluorobenzoyl)thioureido)-5,5-dimethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate

Product 1

HCID 533019352-(3-(2-fluorobenzoyl)thioureido)-5,5-dimethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylic acidYield 33.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To tert-butyl 2-(3-(2-fluorobenzoyl)thioureido)-5,5-dimethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate (36 mg, 0.077 mmol) was added a solution of 2,2,2-trifluoroacetic acid (0.75 mL, 9.76 mmol) in CH2Cl2 (1.1 mL) [40% v/v] and the mixture stirred at RT for 1 h. The solvent was evaporated in vacuo and the residue chromatographed using reversed-phase MPLC (0-100% ACN—H2O; 40 g C18 column) to yield 2-(3-(2-fluorobenzoyl)thioureido)-5,5-dimethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylic acid (10.5 mg, 0.026 mmol, 33% yield) as a pale yellow solid. 1H NMR (500 MHz, DMSO) δ 14.70 (s, 1H), 11.94 (s, 1H), 7.72 (apparent d, J=7.3, 1H), 7.65 (s, 1H), 7.38-7.32 (m, 2H), 4.65 (s, 2H), 2.73 (s, 2H), 1.22 (s, 6H). 13C NMR (126 MHz, DMSO) δ 173.69, 165.48, 163.91, 160.34, 158.35, 146.81, 134.19, 134.12, 130.50, 129.19, 124.64, 124.61, 124.24, 122.28, 122.17, 116.60, 116.32, 116.14, 70.20, 58.87, 37.32, 26.23. LCMS retention time: 3.275 min; LCMS purity at 214 nm=99.6%. HRMS m/z calculated for C18H18FN2O4S2 [M++1]: 409.0687. found 409.0687. Melting point 202.8° C., decomposition.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue chromatographed

Sources & evidence

ORD record
ord-924f20bd7a7544d78f333eef025fdf96
Source dataset
uspto-grants-2016_06
Patent number
US09376452B2

Reaction notes

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