Hydrochloric Acid → HCID 66548856, compound

HRID 2174365Notes

Reaction equation

HRID 2174365 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.CC[N:35]([CH:39]([CH3:41])[CH3:40])C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.C1(N)CC1>CN(C=O)C>[CH:39]1([NH:35][C:6]([CH:4]2[CH2:3][C:2]([OH:1])([C:9]3[CH:14]=[CH:13][C:12]([C:15]4[CH2:19][C:18]([C:24]5[CH:25]=[C:26]([Cl:32])[C:27]([Cl:31])=[C:28]([Cl:30])[CH:29]=5)([C:20]([F:23])([F:21])[F:22])[O:17][N:16]=4)=[CH:11][CH:10]=3)[CH2:5]2)=[O:7])[CH2:41][CH2:40]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707791HCID 86707791, compound

Product 1

HCID 66548856HCID 66548856, compound

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, 0.1 g, 0.196 mmol) in DMF (3 mL) was added DIPEA (0.051 g, 0.393 mmol), HOBt (0.027 g, 0.196 mmol), EDCl.HCl (0.057 g, 0.294 mmol) and cyclopropyl amine (0.011 g, 0.196 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 (5×20 mL). Combined organic layer was washed with saturated NaHCO3 (2×50 mL), dried over sodium sulphate and evaporated in vacuo to get 0.2 g (crude). Crude was purified by column chromatography on silica gel (100-200 mesh). Compound was eluted using 0.7% methanol in DCM to afford off white solid (0.055 g, 51%. 1H-NMR (400 MHz, CDCl3) δ: 0.54-0.59 (m, 2H), 0.81-0.86 (m, 2H), 2.48-2.51 (m, 2H), 2.75-2.86 (m, 4H), 3.67 (d, 1H, J=17.16 Hz), 4.07 (d, 1H, J=17.16 Hz), 5.73 (s, 1H), 5.79 (bs, 1H), 7.54 (d, 2H, J=8.2 Hz), 7.62-7.63 (m, 4H); LC-MS (m/z): [M−H] 544.70,

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 (5×20 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 0.2 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 (0.055 g, 51%

Sources & evidence

ORD record
ord-d2fb4e87bf6240afa90e587a18a6102c
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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