Potassium Carbonate → HCID 86702839, compound

HRID 1427812Notes

Reaction equation

HRID 1427812 reaction equation
[NH2:1][CH2:2][C:3]12[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH2:4]1)[CH2:10]2.[Cl:13][C:14]1[C:15](F)=[CH:16][C:17]([F:27])=[C:18]([CH:26]=1)[C:19]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])=[O:20].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O1CCCC1>[C:3]12([CH2:2][NH:1][C:15]3[C:14]([Cl:13])=[CH:26][C:18]([C:19]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])=[O:20])=[C:17]([F:27])[CH:16]=3)[CH2:12][CH:7]3[CH2:6][CH:5]([CH2:11][CH:9]([CH2:8]3)[CH2:10]1)[CH2:4]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86625Tricyclo(3.3.1.13,7)dec-1-ylmethylamineHCID 580424175-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide

Product 1

HCID 86702839HCID 86702839, compoundYield 8.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A stirred mixture of 1-(aminomethyl)adamantane (0.31 g, 1.85 mmol), 5-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide (0.5 g, 1.85 mmol) and potassium carbonate (0.64 g, 4.63 mmol) in N,N-dimethylformamide (18 mL) and tetrahydrofuran (10 mL) was heated at 65° C. for 48 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was diluted with saturated aqueous ammonium chloride (50 mL) and ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 0 to 10% gradient of methanol in dichloromethane to afford the title compound as a pale yellow solid (0.064 g, 8%): 1H NMR (300 MHz, CDCl3) δ 8.55-8.08 (m, 2H), 7.51-7.40 (m, 1H), 6.58-6.43 (m, 1H), 3.44 (s, 3H), 2.84-2.75 (m, 2H), 2.02 (br s, 3H), 1.81-1.46 (m, 12H); 13C NMR (75 MHz, CDCl3) δ 166.5, 162.5 (d, 1JC-F=255.0 Hz), 153.1 (d, JC-F=11.8 Hz), 130.9 (d, JC-F=3.2 Hz), 106.8, 106.2 (d, JC-F=19.5 Hz), 99.6 (d, 2JC-F=25.3 Hz), 55.7, 42.1, 40.6, 36.9, 33.8, 28.2; MS (ES+) m/z 414.8, 416.8 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. additionThe filtrate was diluted with saturated aqueous ammonium chloride (50 mL) and ethyl acetate (100 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  6. washThe combined organic layers were washed with water (100 mL), brine (100 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography
  11. washeluting with a 0 to 10% gradient of methanol in dichloromethane

Sources & evidence

ORD record
ord-3202196862af470f90820befaff1bd68
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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