Hydrochloric Acid → [2-(2-Difluoromethoxy-phenyl)-5-(6-methyl-pyridin-3-yl)-[1,3,4]thiadiazol-3-yl]-(2-hydroxy-phenyl)-methanone

HRID 1046944Notes

Reaction equation

HRID 1046944 reaction equation
[F:1][CH:2]([F:34])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]1[N:14]([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23]C(=O)C)=[O:16])[N:13]=[C:12]([C:27]2[CH:28]=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=2)[S:11]1.FC(F)OC1C=CC=CC=1C1N(C(C2C(F)=CC(F)=CC=2F)=O)N=C(C2C=NC(C)=CC=2)S1.[Li+].[OH-].Cl>C1COCC1.CO>[F:34][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]1[N:14]([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[OH:23])=[O:16])[N:13]=[C:12]([C:27]2[CH:28]=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=2)[S:11]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 58025821HCID 58025821, compoundHCID 67279527(2-(2-(Difluoromethoxy)phenyl)-5-(6-methylpyridin-3-yl)-1,3,4-thiadiazol-3(2H)-yl)(2-acetoxyphenyl)methanone

Product 1

HCID 58025703[2-(2-Difluoromethoxy-phenyl)-5-(6-methyl-pyridin-3-yl)-[1,3,4]thiadiazol-3-yl]-(2-hydroxy-phenyl)-methanone

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

(2-(2-(Difluoromethoxy)phenyl)-5-(6-methylpyridin-3-yl)-1,3,4-thiadiazol-3(2H)-yl)(2-acetoxyphenyl)methanone (0.02 mmol) prepared in a similar manner as described in experiment 11 for [2-(2-difluoromethoxy-phenyl)-5-(6-methyl-pyridin-3-yl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone, is dissolved in THF/MeOH (1 mL/0.5 mL) and treated with aqueous LiOH (1 M) (0.5 mL) at room temperature for 30 minutes. Aqueous HCl (3 M) is added to adjust the pH to 5-6. Solvent is removed and the residue is purified by preparative HPLC (20-100% MeCN/H2O) to yield [2-(2-difluoromethoxy-phenyl)-5-(6-methyl-pyridin-3-yl)-[1,3,4]thiadiazol-3-yl]-(2-hydroxy-phenyl)-methanone: 1H NMR (400 MHz, CDCl3) 9.02 (d, J=2.0 Hz, 1H), 8.41 (d, J=8.6 Hz, 1H), 8.23 (dd, J1=8.2 Hz, J2=2.2 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.65 (s, 1H), 7.62 (dd, J1=7.8 Hz, J2=1.3 Hz, 1H), 7.45-7.53 (m, 5H), 6.97-7.01 (m, 2H), 2.79 (s, 3H); LC/MS (ES+): (M+1) 442.1.

Workup

  1. customSolvent is removed
  2. customthe residue is purified by preparative HPLC (20-100% MeCN/H2O)

Sources & evidence

ORD record
ord-c0d9d334ac594c5d9b95e9b969ead850
Source dataset
uspto-grants-2013_10
Patent number
US08569345B2

Reaction notes

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