Hydrochloric Acid → HCID 72548903, compound

HRID 1849872Notes

Reaction equation

HRID 1849872 reaction equation
[CH2:1]([O:5][C:6]1[C:14]([CH:15]2[CH2:17][CH2:16]2)=[CH:13][C:9]([C:10]([OH:12])=O)=[C:8]([F:18])[CH:7]=1)[CH2:2][CH2:3][CH3:4].C(N1C=CN=C1)(N1C=CN=C1)=O.N12CCCN=C1CCCCC2.[CH:42]1([S:45]([NH2:48])(=[O:47])=[O:46])[CH2:44][CH2:43]1.Cl>O1CCCC1>[CH2:1]([O:5][C:6]1[C:14]([CH:15]2[CH2:17][CH2:16]2)=[CH:13][C:9]([C:10]([NH:48][S:45]([CH:42]2[CH2:44][CH2:43]2)(=[O:47])=[O:46])=[O:12])=[C:8]([F:18])[CH:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 86703758HCID 86703758, compound

Product 1

HCID 72548903HCID 72548903, compoundYield 20.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 4-butoxy-5-cyclopropyl-2-fluorobenzoic acid (0.039 g, 0.15 mmol) in tetrahydrofuran (1 mL) and under an atmosphere of nitrogen was added carbonyldiimidazole (0.030 g, 0.18 mmol) and the reaction mixture was stirred at 70° C. for 1 hour. The mixture was cooled down to room temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.02 mL, 0.02 mmol) was added followed by cyclopropanesulfonamide (0.024 g, 0.20 mmol) and the stirring continued at ambient temperature for 18 hours. 5% aqueous hydrochloric acid solution (0.15 mL) was added and the mixture was concentrated and directly purified by column chromatography (0 to 30% gradient ethyl acetate in hexanes) to afford the title compound (0.011 g, 20%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.82-8.57 (m, 1H), 7.57 (d, J=9.24 Hz, 1H), 6.58 (d, J=14.42 Hz, 1H), 4.04 (t, J=6.30, 6.30 Hz, 2H), 3.16-3.05 (m, 1H), 2.18-1.74 (m, 3H), 0.72-0.61 (m, 2H), 1.71-0.84 (m, 13H), 0.74-0.60 (m, 2H); MS (ES+) m/z 356.1 (M+1); MS (ES−) m/z 354.2 (M−1).

Workup

  1. temperatureThe mixture was cooled down to room temperature
  2. waitthe stirring continued at ambient temperature for 18 hours
  3. concentrationthe mixture was concentrated
  4. customdirectly purified by column chromatography (0 to 30% gradient ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7fad296e9055407dac0eb00d9fb82c93
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

Loading…