Hydrochloric Acid → HCID 66548859, compound

HRID 2174372Notes

Reaction equation

HRID 2174372 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 7, 0.1 g, 0.195 mmol) in DMF (3 mL) was added HOBt (0.026 g, 0.195 mmol), DIPEA (0.051 g, 0.391 mmol) followed by addition of EDCl.HCl (0.056 g, 0.293 mmol) and cyclopropyl amine (0.011 g, 0.195 mmol) at room temperature. 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 (20 mL) and extracted with EtOAc (5×20 mL). Combined organic layer was washed with saturated water (100 mL), brine (100 mL), dried over sodium sulphate and evaporated in vacuo to get a yellow semisolid (0.108 g, crude). Crude was purified by column chromatography on silica gel (100-200 mesh). Compound was eluted using 0.5% methanol in DCM to afford off white solid (0.020 g, 19%, CR963-125249-74-1). 1H-NMR (400 MHz, CDCl3) δ: 0.49-0.51 (m, 2H), 0.76-0.81 (m, 2H), 2.52-2.58 (m, 1H), 2.67-2.76 (m, 3H), 2.93-3.06 (m, 2H), 3.68 (d, 1H, J=17.04 Hz), 4.08 (d, 1H, J=17.16 Hz), 5.55 (bs, 1H), 7.51 (d, 2H, J=8.08 Hz), 7.63 (s, 2H), 7.68 (d, 2H, J=8.20 Hz); LC-MS (m/z): [M−H] 546.80.

Workup

  1. customat room temperature
  2. customResulting
  3. customreaction mixture
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (20 mL)
  6. extractionextracted with EtOAc (5×20 mL)
  7. washCombined organic layer was washed with saturated water (100 mL), brine (100 mL)
  8. dry with materialdried over sodium sulphate
  9. customevaporated in vacuo
  10. customto get a yellow semisolid (0.108 g, crude)
  11. customCrude was purified by column chromatography on silica gel (100-200 mesh)
  12. washCompound was eluted
  13. customto afford off white solid (0.020 g, 19%, CR963-125249-74-1)

Sources & evidence

ORD record
ord-4a4ef97ae7424412a346eafe803c9fad
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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