Hydrochloric Acid → HCID 72548901, compound

HRID 1849865Notes

Reaction equation

HRID 1849865 reaction equation
[CH:1]1([C:4]2[C:5]([O:14][CH2:15][CH:16]3[CH:21]([CH3:22])[CH2:20][CH2:19][CH2:18][CH:17]3[CH3:23])=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9](O)=[O:10])[CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.N12CCCN=C1CCCCC2.[N:47]1([S:51]([NH2:54])(=[O:53])=[O:52])[CH2:50][CH2:49][CH2:48]1.Cl>O1CCCC1>[N:47]1([S:51]([NH:54][C:9](=[O:10])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[C:5]([O:14][CH2:15][CH:16]3[CH:21]([CH3:22])[CH2:20][CH2:19][CH2:18][CH:17]3[CH3:23])=[CH:6][C:7]=2[F:13])(=[O:53])=[O:52])[CH2:50][CH2:49][CH2:48]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 450805661-AzetidinesulfonamideHCID 86703752HCID 86703752, compound

Product 1

HCID 72548901HCID 72548901, compoundYield 22.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 5-cyclopropyl-4-((2,6-dimethylcyclohexyl)methoxy)-2-fluorobenzoic acid (0.07 g, 0.22 mmol) in tetrahydrofuran (2 mL) and under an atmosphere of nitrogen was added carbonyldiimidazole (0.053 g, 0.33 mmol) and the reaction mixture was stirred at 70° C. for 1 hour. The mixture was cooled down to ambient temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.07 mL, 0.45 mmol) was added followed by azetidine-1-sulfonamide (0.051 g, 0.37 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% ethyl acetate in hexanes) to afford the title compound (0.022 g, 22%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.75-8.55 (m, 1H), 7.57 (d, J=9.1 Hz, 1H), 6.62 (d, J=14.5 Hz, 1H), 4.23 (t, J=7.7 Hz, 4H), 4.01 (d, J=4.5 Hz, 2H), 2.35-2.17 (m, 2H), 2.07-1.95 (m, 2H), 1.86-0.56 (m, 20H); MS (ES+) m/z 439.1 (M+1); MS (ES−) m/z 437.2 (M−1).

Workup

  1. temperatureThe mixture was cooled down to ambient 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% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1aa16fcecb3040cfafad374fb50879d7
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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