Potassium Carbonate → HCID 86723794, compound

HRID 577568Notes

Reaction equation

HRID 577568 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]([CH2:13][C:14]3[C:15](=[O:22])[NH:16][C:17]([CH3:21])=[CH:18][C:19]=3[CH3:20])[CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[CH:4][C:3]=1[OH:24].[F:25][C:26]([F:40])([F:39])[CH2:27]OS(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]([CH2:13][C:14]3[C:15](=[O:22])[NH:16][C:17]([CH3:21])=[CH:18][C:19]=3[CH3:20])[CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[CH:4][C:3]=1[O:24][CH2:27][C:26]([F:40])([F:39])[F:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 67942Ethanol, 2,2,2-trifluoro-, 1-(4-methylbenzenesulfonate)HCID 86723792HCID 86723792, compound

Product 1

HCID 86723794HCID 86723794, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 6-chloro-4-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-hydroxy-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (124d, 100 mg, 0.287 mmol), toluene-4-sulfonic acid 2,2,2-trifluoro-ethyl ester (73.0 mg, 0.287 mmol), potassium carbonate (79.0 mg, 0.574 mmol), and anhydrous DMF (6 mL) was heated at 150° C. for 45 minutes in the microwave. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was separated, washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, and concentrated under vacuum. The residue was purified by column chromatography (silica gel, MeOH/EtOAc) to give the title compound (Example 124, 18 mg, 16% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.62 (br. s., 1H), 7.33 (d, J=8.93 Hz, 1H), 7.05 (d, J=8.93 Hz, 1H), 5.94 (s, 1H), 4.84 (q, J=8.60 Hz, 2H), 4.62 (s, 2H), 4.02 (br. s., 2H), 3.41 (br. s., 2H), 2.21 (s, 3H), 2.14 (s, 3H); MS 431.1 [M+1].

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL)
  3. customThe organic phase was separated
  4. washwashed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by column chromatography (silica gel, MeOH/EtOAc)

Sources & evidence

ORD record
ord-d5f9db91fa6343d4b6fa46219987bbc7
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

Loading…