Hydrochloric Acid → HCID 66549428, compound

HRID 2174390Notes

Reaction equation

HRID 2174390 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[N:26]1[CH2:29][CH:28]([C:30](O)=[O:31])[CH2:27]1.CCN=C=N[CH2:38][CH2:39][CH2:40][N:41](C)C.Cl.Cl.CCN(C(C)C)C(C)C.C1(N)CC1>CN(C=O)C>[CH:40]1([NH:41][C:30]([CH:28]2[CH2:27][N:26]([C:3]3[CH:4]=[CH:5][C:6]([C:8]4[CH2:12][C:11]([C:17]5[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=5)([C:13]([F:14])([F:16])[F:15])[O:10][N:9]=4)=[CH:7][C:2]=3[Cl:1])[CH2:29]2)=[O:31])[CH2:38][CH2:39]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707798HCID 86707798, compound

Product 1

HCID 66549428HCID 66549428, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-{2-chloro-4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-azetidine-3-carboxylic acid (Preparation 14, 0.1 g, 0.190 mmol) in dry DMF (3 mL) was added EDCl.HCl (0.055 g, 0.280 mmol), DIPEA (0.049 g, 0.380 mmol) and cyclopropyl amine (0.011 g, 0.190 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 EtOAc (10 mL). Organic layer was washed with saturated solution of lithium chloride (3×20 mL), water (2×20 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 0.8% methanol in DCM to afford sticky mass, which was crystallized by chloroform:pentane (1:9) to afford off white solid (0.020 g, 20%). 1H-NMR (400 MHz, CDCl3) δ: 0.50-0.53 (m, 2H), 0.77-0.82 (m, 2H), 2.72-2.76 (m, 1H), 3.26-3.30 (m, 1H), 3.60 (d, 1H, J=17.12 Hz), 4.00 (d, 1H, J=17 Hz), 4.23-4.33 (m, 4H), 5.72 (bs, 1H), 6.47 (d, 1H, J=8.6 Hz), 7.40 (dd, 1H, J1=8.44 Hz, J2=1.88 Hz), 7.46 (d, 1H, J=1.8 Hz), 7.62 (s, 2H); LC-MS (m/z): [M−H] 563.50.

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 EtOAc (10 mL)
  7. washOrganic layer was washed with saturated solution of lithium chloride (3×20 mL), water (2×20 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 sticky mass, which
  14. customwas crystallized by chloroform:pentane (1:9)

Sources & evidence

ORD record
ord-b172cc1a9bdb4cdebed81826d114186d
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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