Trifluoroacetic acid → HCID 58025839, compound

HRID 1694364Notes

Reaction equation

HRID 1694364 reaction equation
C(O[C:6]([NH:8][NH:9][C:10]([C:12]1[CH:13]=[N:14][C:15]([F:18])=[CH:16][CH:17]=1)=[S:11])=[O:7])(C)(C)C.C(OC(NNC(=O)C1C=CC(F)=CC=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C1(SC)C=CC=CC=1.CCN(C(C)C)C(C)C.[F:61][CH:62]([F:72])[O:63][C:64]1[CH:71]=[CH:70][CH:69]=[CH:68][C:65]=1[CH:66]=O.[F:73][C:74]1[CH:82]=[C:81]([F:83])[CH:80]=[C:79]([F:84])[C:75]=1C(Cl)=O>C(Cl)Cl>[F:61][CH:62]([F:72])[O:63][C:64]1[CH:71]=[CH:70][CH:69]=[CH:68][C:65]=1[CH:66]1[N:8]([C:6]([C:75]2[C:74]([F:73])=[CH:82][C:81]([F:83])=[CH:80][C:79]=2[F:84])=[O:7])[N:9]=[C:10]([C:12]2[CH:13]=[N:14][C:15]([F:18])=[CH:16][CH:17]=2)[S:11]1

Participants

9

Reactant 7

HCID 6422Trifluoroacetic acidHCID 7520ThioanisoleHCID 81531DiisopropylethylamineHCID 1448952,4,6-Trifluorobenzoyl chlorideHCID 27369842-(Difluoromethoxy)benzaldehydeHCID 67279032tert-Butyl 2-(4-fluorobenzoyl)hydrazine-1-carboxylateHCID 86637599HCID 86637599, compound

Product 1

HCID 58025839HCID 58025839, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N′-(6-fluoro-pyridine-3-carbothioyl)-hydrazinecarboxylic acid tert-butyl ester (0.044 mmol) prepared as described in example 3 for N′-(4-fluoro-benzoyl)-hydrazinecarboxylic acid tert-butyl ester, is treated with TFA (0.44 mmol) and thioanisole (0.44 mmol) in dry CH2Cl2 (1 mL) at room temperature for 30 minutes. The solvent is removed and the residue is dissolved in dry CH2Cl2 (1 mL). DIEA (0.22 mmol) is added to the solution and the mixture is treated with 2-difluoromethoxy-benzaldehyde (0.067 mmol) in the presence of 4 Å molecular sieves. 2,4,6-Trifluorobenzoyl chloride (0.089 mmol) is added after 5 minutes. The mixture is kept at room temperature for 16 hours and purified by preparative silica gel TLC (30% EtOAc/hexane) to yield [2-(2-difluoromethoxy-phenyl)-5-(6-fluoro-pyridin-3-yl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone: 1H NMR (400 MHz, CDCl3) 8.39 (s, 1H), 7.93-7.97 (m, 1H), 7.54 (s, 1H), 7.37-7.41 (m, 2H), 7.24-7.27 (m, 1H), 7.19 (d, J=8.1 Hz, 1H), 6.97 (dd, J1=8.6 Hz, J2=2.7 Hz, 1H), 6.78 (t, J=8.3 Hz, 2H), 6.67 (dd, J1=75.0 Hz, J2=71.7 Hz, 1H); LC/MS (ES+): (M+1) 484.1.

Workup

  1. customThe solvent is removed
  2. dissolutionthe residue is dissolved in dry CH2Cl2 (1 mL)
  3. custompurified by preparative silica gel TLC (30% EtOAc/hexane)

Sources & evidence

ORD record
ord-6416c6ac846c40bd9fe35aaf76e3b4a9
Source dataset
uspto-grants-2012_04
Patent number
US08158662B2

Reaction notes

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