1,4-Dioxane → HCID 44554596, compound

HRID 1254068Notes

Reaction equation

HRID 1254068 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12](I)=[N:11][C:10]=2[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.C[C:27]1[C:28](B(O)O)=[N:29][NH:30][CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:44]1>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12]([C:27]3[CH:28]=[N:29][N:30]([CH3:44])[CH:31]=3)=[N:11][C:10]=2[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 58497179HCID 58497179, compoundHCID 178430905HCID 178430905, compound

Product 1

HCID 44554596HCID 44554596, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of Example 133 compound (60 mg, 0.119 mmol), methylpyrazole boronic acid (29.7 mg, 0.143 mmol), Pd(PPh3)4 (13.7 mg, 0.012 mmol), K3PO4 (50.5 mg, 0.238 mmol, aq) in dioxane (2 ml) was vacuumed and purged to N2 for 3 times, then reaction mixture was heated at 110° C. for 3 hrs. Reaction mixture was diluted with EtOAc, washed with brine dried and concentrated. Separated by prep TLC (hex:EtOAc:CH3OH=6:5:1) to give 4-{5-[(4-chlorophenyl)sulfanyl]-1-methyl-4-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl}-1-methyl-1H-pyrazole (25 mg) 1H NMR (500 MHz), [(CDCl3]: 8.35 (m, 1H), 7.95 (m, 3H), 7.25 (m, 3H), 7.01 (m, 2H), 4.10 (s, 3H), 3.78 (s, 3H), 3.10 (s, 3H). LCMS: [M+1]+=459.0. Human FAAH lysate assay: IC50=13.9 nM.

Workup

  1. custompurged to N2 for 3 times
  2. customreaction mixture
  3. customReaction mixture
  4. washwashed with brine
  5. customdried
  6. concentrationconcentrated
  7. customSeparated by prep TLC (hex:EtOAc:CH3OH=6:5:1)

Sources & evidence

ORD record
ord-27304e4989dc405994e16b2524b2a737
Source dataset
uspto-grants-2013_06
Patent number
US08455528B2

Reaction notes

Loading…