Hydrochloric Acid → HCID 66549041, compound

HRID 2174373Notes

Reaction equation

HRID 2174373 reaction equation
[F: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]([OH:8])=O)[CH2:3]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.Cl.[F:66][C:67]([F:71])([F:70])[CH2:68][NH2:69]>CN(C=O)C>[F:66][C:67]([F:71])([F:70])[CH2:68][NH:69][C:6]([CH:4]1[CH2:5][C:2]([F: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:22])([F:23])[F:21])[O:17][N:16]=3)=[CH:11][CH:10]=2)[CH2:3]1)=[O:8]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707793HCID 86707793, compound

Product 1

HCID 66549041HCID 66549041, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-Fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (Preparation 6, 0.1 g, 0.195 mmol) in DMF (3 mL) was added HOBt (0.027 g, 0.195 mmol) and DIPEA (0.050 g, 0.391 mmol) followed by addition of EDCl.HCl (0.056 g, 0.292 mmol) and 2,2,2-trifluoro-ethylamine hydrochloride (0.026 g, 0.195 mmol) at 0° C. Resulting reaction mixture was stirred at room temperature for 16 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (50 mL) and extracted with EtOAc (3×20 mL). Combined organic layer was washed with saturated NaHCO3 (2×50 mL), dried over sodium sulphate and evaporated in vacuo to get 0.150 g crude. Crude was purified by column chromatography on silica gel (100-200 mesh size). Compound was eluted using 0.8% methanol in DCM to afford white solid (0.060 g, 52%). 1H-NMR (400 MHz, CDCl3) δ: 2.80-2.90 (m, 3H), 2.91-2.98 (m, 1H), 3.30-3.39 (m, 1H), 3.67 (d, 1H, J=17.16 Hz), 3.90-3.99 (m, 2H), 4.07 (d, 1H, J=17.16 Hz), 5.71 (bs, 1H), 7.53 (d, 2H, J=8.32 Hz), 7.64-7.67 (m, 4H); LC-MS (m/z): [M−H] 588.70.

Workup

  1. customat 0° C
  2. customResulting
  3. customreaction mixture
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (50 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. washCombined organic layer was washed with saturated NaHCO3 (2×50 mL)
  8. dry with materialdried over sodium sulphate
  9. customevaporated in vacuo
  10. customto get 0.150 g crude
  11. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  12. washCompound was eluted

Sources & evidence

ORD record
ord-47ec2ef5c3d7442995c2e541f7bb9820
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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