Hydrochloric Acid → HCID 60202402, compound

HRID 2174364Notes

Reaction equation

HRID 2174364 reaction equation
[OH:1][C:2]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:29]=[C:28]([Cl:30])[C:27]([Cl:31])=[C:26]([Cl:32])[CH:25]=4)([C:20]([F:23])([F:22])[F:21])[O:17][N:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH:4]([C:6](O)=[O:7])[CH2:3]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.Cl.[F:54][C:55]([F:59])([F:58])[CH2:56][NH2:57]>CN(C=O)C>[F:54][C:55]([F:59])([F:58])[CH2:56][NH:57][C:6]([CH:4]1[CH2:5][C:2]([OH:1])([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:25]=[C:26]([Cl:32])[C:27]([Cl:31])=[C:28]([Cl:30])[CH:29]=4)([C:20]([F:21])([F:22])[F:23])[O:17][N:16]=3)=[CH:11][CH:10]=2)[CH2:3]1)=[O:7]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 86707791HCID 86707791, compound

Product 1

HCID 60202402HCID 60202402, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (Preparation 4, 0.050 g, 0.098 mmol) in DMF (0.5 mL) was added HOBt (0.013 g, 0.096 mmol), DIPEA (0.025 g, 0.193 mmol) EDCl.HCl (0.019 g, 0.099 mmol) and 2,2,2-Trifluoro-ethylamine hydrochloride (0.013 g, 0.096 mmol) at 0° C. Resulting reaction mixture was stirred at room temperature for 18 h under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (5 mL) and extracted with EtOAc (2×5 mL). Combined organic layer was washed with brine (5 mL), dried over sodium sulphate and evaporated in vacuo to get thick oil, 0.093 mg crude. Crude was purified by column chromatography on silica gel (100-200 mesh size). Compound was eluted using 2% methanol in DCM to afford thick yellow oil, which was re-purified by DCM in pentane (1:9) to afford white solid (0.020 g, 37.5%). 1H-NMR (400 MHz, CDCl3) δ: 2.55-2.57 (m, 2H), 2.87-2.91 (m, 3H), 3.67 (d, 1H, J=17.24), 3.96-4.01 (m, 2H), 4.08 (d, 1H, J=17.2 Hz), 4.71 (s, 1H), 5.97 (t, 1H, J=6.32 Hz), 7.55 (d, 2H, J=8.44 Hz), 7.64-7.6 (m, 4H). LC-MS (m/z): [M−H] 586.90.

Workup

  1. customat 0° C
  2. customResulting
  3. customreaction mixture
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (5 mL)
  6. extractionextracted with EtOAc (2×5 mL)
  7. washCombined organic layer was washed with brine (5 mL)
  8. dry with materialdried over sodium sulphate
  9. customevaporated in vacuo
  10. customto get thick oil, 0.093 mg crude
  11. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  12. washCompound was eluted
  13. customto afford thick yellow oil, which
  14. customwas re-purified by DCM in pentane (1:9)

Sources & evidence

ORD record
ord-8211ac1d489647bd9f61a8439ff9a29d
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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