Hydrochloric Acid → HCID 67279300, compound

HRID 1694348Notes

Reaction equation

HRID 1694348 reaction equation
C(O[C:6]([NH:8][NH:9][C:10](=[S:18])[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=O)(C)(C)C.[CH3:19][O:20][C:21]1[C:22]([O:29][Si:30]([CH:37]([CH3:39])[CH3:38])([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])[CH3:32])=[C:23]([CH:26]=[CH:27][CH:28]=1)C=O.CCN(C(C)C)C(C)C.[F:49][C:50]1[CH:58]=[C:57]([F:59])[CH:56]=[C:55]([F:60])[C:51]=1[C:52](Cl)=[O:53].Cl>C(Cl)Cl.CCOC(C)=O>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[S:18][CH:6]([C:28]3[CH:27]=[CH:26][CH:23]=[C:22]([O:29][Si:30]([CH:31]([CH3:32])[CH3:33])([CH:34]([CH3:36])[CH3:35])[CH:37]([CH3:38])[CH3:39])[C:21]=3[O:20][CH3:19])[N:8]([C:52]([C:51]3[C:50]([F:49])=[CH:58][C:57]([F:59])=[CH:56][C:55]=3[F:60])=[O:53])[N:9]=2)=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 1448952,4,6-Trifluorobenzoyl chlorideHCID 58025809HCID 58025809, compoundHCID 866375961,1-Dimethylethyl 2-[(4-fluorophenyl)thioxomethyl]hydrazinecarboxylate

Product 1

HCID 67279300HCID 67279300, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.23 mmol) is dissolved in 5 mL of CH2Cl2 at room temperature in a dry round bottom flask. Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature. The reaction is complete after 30 minutes as determined by LC/MS. Solvent is removed in vacuo. The resultant oil is dried on the vacuum line for 30 minutes and dissolved in 1 mL of dry CH2Cl2. This solution is added to a mixture of 3-methoxy-2-triisopropylsilanyloxy-benzaldehyde (1.23 mmol) and DIEA (4.9 mmol) in 1 mL of dry CH2Cl2. The mixture is allowed to stand at room temperature in the presence of molecular sieves for 5 minutes. 2,4,6-Trifluorobenzoyl chloride (1.6 mmol) is added and the reaction mixture is kept at room temperature for 16 hours. HCl (1 M) (10 mL) is added to the mixture to quench the reaction. The mixture is diluted with EtOAc (50 mL), washed with HCl (1 M) (2×10 mL) and brine (50 mL) and dried over anhydrous Na2 SO4. Purification is accomplished by silica flash chromatography (5% EtOAc/hexane) to give [5-(4-fluoro-phenyl)-2-(2-methoxy-3-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd, J1=8.8 Hz, J2=5.3 Hz, 2H), 7.51 (s, 1H), 7.04 (t, J=8.6 Hz, 2H), 6.95 (t, J=7.8 Hz, 1H), 6.87 (t, J=8.8 Hz, 2H), 6.77 (t, J=7.9 Hz, 2H), 4.03 (s, 3H), 1.27-1.36 (m, 3H), 1.14 (dd, J1=J2=6.3 Hz, 18H); LC/MS (ES+): (M+1) 309.2. Rf=0.4 (5% EtOAc/hexanes).

Workup

  1. customRemoval of the ester group
  2. additionis accomplished adding TFA (2 mL) to the solution at room temperature
  3. customSolvent is removed in vacuo
  4. customThe resultant oil is dried on the vacuum line for 30 minutes
  5. dissolutiondissolved in 1 mL of dry CH2Cl2
  6. waitto stand at room temperature in the presence of molecular sieves for 5 minutes
  7. waitthe reaction mixture is kept at room temperature for 16 hours
  8. customto quench
  9. customthe reaction
  10. washwashed with HCl (1 M) (2×10 mL) and brine (50 mL)
  11. customdried over anhydrous Na2 SO4
  12. customPurification

Sources & evidence

ORD record
ord-b221ce20fc8340099013af71b670ca9f
Source dataset
uspto-grants-2012_04
Patent number
US08158662B2

Reaction notes

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