Hydrochloric Acid → HCID 66549231, compound

HRID 2174383Notes

Reaction equation

HRID 2174383 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]([OH:27])=O)[CH2:22]4)=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].C1C=C[C:35]2N(O)N=[N:38][C:36]=2[CH:37]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.C1(N)CC1>CN(C=O)C>[CH:36]1([NH:38][C:25]([CH:23]2[CH2:22][N:21]([C:18]3[CH:19]=[CH:20][C:15]([C:12]4[CH2:11][C:10]([C:4]5[CH:5]=[C:6]([Cl:9])[C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=5)([C:28]([F:30])([F:31])[F:29])[O:14][N:13]=4)=[CH:16][CH:17]=3)[CH2:24]2)=[O:27])[CH2:37][CH2:35]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707796HCID 86707796, compound

Product 1

HCID 66549231HCID 66549231, compoundYield 33.3%

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 HOBt (0.027 g, 0.203 mmol), DIPEA (0.052 g, 0.406 mmol), EDCl.HCl (0.058 g, 0.304 mmol) and cyclopropyl amine (0.011 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 (20 mL) and extracted with EtOAc (3×20 mL). Combined organic layer was washed with saturated NaHCO3 (2×50 mL), water (2×50 mL), brine (50 mL), dried over sodium sulphate and evaporated in vacuo to crude. Crude was purified by column chromatography on silica gel (100-200 mesh size). Compound was eluted using 1.1% methanol in DCM to afford white solid (0.036 g, 33%). 1H-NMR (400 MHz, CDCl3) δ: 0.49-0.53 (m, 2H), 0.77-0.87 (m, 2H), 2.74-2.77 (m, 1H), 3.31-3.34 (m, 1H), 3.61 (d, 1H, J=16.88 Hz), 4.01-4.07 (m, 5H), 5.72 (bs, 1H), 6.40 (d, 2H, J=8.68 Hz), 7.47 (d, 2H, J=8.68 Hz), 7.63 (s, 2H). LC-MS (m/z): [M−H] 529.70.

Workup

  1. customat 0° C
  2. customResulting
  3. customreaction mixture
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (20 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. washCombined organic layer was washed with saturated NaHCO3 (2×50 mL), water (2×50 mL), brine (50 mL)
  8. dry with materialdried over sodium sulphate
  9. customevaporated in vacuo to crude
  10. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  11. washCompound was eluted

Sources & evidence

ORD record
ord-b62e7eba01f2472c930191808b3f8075
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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