Hydrochloric Acid → HCID 66548859, compound

HRID 2174371Notes

Reaction equation

HRID 2174371 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=C[C:36]2N(O)N=[N:39][C:37]=2[CH:38]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.C1(N)CC1>CN(C=O)C>[CH:37]1([NH:39][C:6]([CH:4]2[CH2:5][C:2]([F:1])([C:9]3[CH:10]=[CH:11][C:12]([C:15]4[CH2:19][C:18]([C:24]5[CH:29]=[C:28]([Cl:30])[C:27]([Cl:31])=[C:26]([Cl:32])[CH:25]=5)([C:20]([F:21])([F:22])[F:23])[O:17][N:16]=4)=[CH:13][CH:14]=3)[CH2:3]2)=[O:8])[CH2:38][CH2:36]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707793HCID 86707793, compound

Product 1

HCID 66548859HCID 66548859, compound

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, 0.080 g, 0.156 mmol) in DMF (2 mL) was added HOBt (0.022 g, 0.156 mmol), DIPEA (0.040 g, 0.302 mmol) followed by addition of EDCl.HCl (0.045 g, 0.256 mmol) and cyclopropyl amine (0.009 g, 0.156 mmol) at 0° C. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (10 mL), extracted with ethyl acetate (2×10 mL). Combined organic layer was washed with brine (20 mL), lithium chloride solution (20 mL), water (20 mL), dried over sodium sulphate and evaporated in vacuo to get crude. Crude was purified by column chromatography on silica gel (100-200 mesh size). Compound was eluted using 1% methanol in DCM to afford thick yellow oil, which was re-purified by DCM in pentane (1:9) to afford white solid (0.035 g, 41%. 1H-NMR (400 MHz, CDCl3) δ: 0.48-0.52 (m, 2H), 0.76-0.81 (m, 2H), 2.69-2.77 (m, 2H), 2.83-2.93 (m, 3H), 3.15-3.23 (m, 1H), 3.67 (d, 1H, J=17.2 Hz), 4.07 (d, 1H, J=17.2 Hz), 5.58 (bs, 1H), 7.56-7.58 (m, 2H), 7.64-7.66 (m, 4H). LC-MS (m/z): [M−H] 546.90.

Workup

  1. customat 0° C
  2. customResulting
  3. customreaction mixture
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (10 mL)
  6. extractionextracted with ethyl acetate (2×10 mL)
  7. washCombined organic layer was washed with brine (20 mL), lithium chloride solution (20 mL), water (20 mL)
  8. dry with materialdried over sodium sulphate
  9. customevaporated in vacuo
  10. customto get 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)
  15. customto afford white solid (0.035 g, 41%

Sources & evidence

ORD record
ord-6d4df60aa5294955a18628ec314a7a2a
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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