Hydrochloric Acid → HCID 66549233, compound

HRID 2174385Notes

Reaction equation

HRID 2174385 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:28]([F:31])([F:30])[F:29])[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:24][CH:23]([C:25](O)=[O:26])[CH2:22]4)=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.Cl.[F:65][C:66]([F:70])([F:69])[CH2:67][NH2:68]>CN(C=O)C>[F:65][C:66]([F:70])([F:69])[CH2:67][NH:68][C:25]([CH:23]1[CH2:22][N:21]([C:18]2[CH:19]=[CH:20][C:15]([C:12]3[CH2:11][C:10]([C:4]4[CH:3]=[C:2]([Cl:1])[C:7]([Cl:8])=[C:6]([Cl:9])[CH:5]=4)([C:28]([F:29])([F:30])[F:31])[O:14][N:13]=3)=[CH:16][CH:17]=2)[CH2:24]1)=[O:26]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707796HCID 86707796, compound

Product 1

HCID 66549233HCID 66549233, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-azetidine-3-carboxylic acid (Preparation 12, 0.1 g, 0.203 mmol) in DMF (3 mL) was added DIPEA (0.052 g, 0.406 mmol), HOBt (0.027 g, 0.203 mmol), EDCl.HCl (0.058 g, 0.304 mmol) and 2,2,2-trifluoro-ethylamine hydrochloride (0.027 g, 0.203 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), 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 0.170 mg 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 pale yellow solid, which was re-purified by DCM in pentane (1:9) to afford pale yellow solid (0.082 g, 71%). 1H-NMR (400 MHz, CDCl3) δ: 3.43-3.48 (m, 1H), 3.62 (d, 1H, J=17.04), 3.93-4.00 (m, 2H), 4.04 (d, 1H, J=17.0), 4.09-4.14 (m, 4H), 5.94 (t, 1H, J=6.06 Hz), 6.43 (d, 2H, J=8.72 Hz), 7.47-7.50 (m, 2H), 7.63 (s, 2H); LC-MS (m/z): [M−H] 571.70.

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 0.170 mg crude
  11. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  12. washCompound was eluted
  13. customto afford pale yellow solid, which
  14. customwas re-purified by DCM in pentane (1:9)

Sources & evidence

ORD record
ord-d0944e57cd4748bd9d79f50a36719b7a
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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