Triethylamine → HCID 178434757, compound

HRID 1159387Notes

Reaction equation

HRID 1159387 reaction equation
[Cl:1][C:2]1[CH:15]=[C:14]([CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([Cl:22])=[CH:12][C:3]=1[O:4][C@H:5]1[CH2:8][C@H:7]([CH2:9][NH:10][CH3:11])[CH2:6]1.C(N(CC)CC)C.[CH3:30][C:31]1[C:35]([C:36](Cl)=[O:37])=[C:34]([CH3:39])[O:33][N:32]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[CH:15]=[C:14]([CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([Cl:22])=[CH:12][C:3]=1[O:4][C@H:5]1[CH2:6][C@H:7]([CH2:9][N:10]([CH3:11])[C:36]([C:35]2[C:31]([CH3:30])=[N:32][O:33][C:34]=2[CH3:39])=[O:37])[CH2:8]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27362653,5-Dimethylisoxazole-4-carbonyl ChlorideHCID 178484148HCID 178484148, compound

Product 1

HCID 178434757HCID 178434757, compoundYield 117.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Example 381, ({trans-3-[2,5-dichloro-4-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl)methylamine (100 mg, 0.29 mmol) and triethylamine (0.04 mL, 0.29 mmol) were dissolved in CH2Cl2 (2 mL). 3,5-Dimethylisoxazole-4-carbonyl chloride (47 mg, 0.29 mmol) was added dropwise under stirring. The mixture was stirred at RT for 3 h and sat. K2CO3 was added. The mixture was stirred at RT for 20 h, dried with Na2SO4, and evaporated. The residue was purified chromatographically (silica gel 40-63 μm, 5 ml, CCl4/CHCl3 100:0→0:100, then CHCl3/MeOH 100:0→95:5). The residue was dissolved in ether (1 mL). 4N HCl/dioxane (0.10 mL) was added, and the reaction mixture was evaporated to dryness, recrystallized from i-PrOH/Et2O. The crystals were separated by filtration and dryed in vacuo to give the title compound (86 mg, 59%) as yellow crystals. LC/MS data: 466.2 (M+H) (calculated for C23H29Cl2N3O3 466.41). 1H NMR-data (DMSO-d6): 10.646 (br.s, 1H, NH+); 7.99 (s, 1H, NH); 6.83-7.24 (m, 1H, Ar—H); 4.66-5.17 (m, 1H), 4.32-4.44 (m, 2H); 3.37-3.72 (m, 4H); 3.03-3.16 (m, 2H); 2.91 (s, 3H); 2.64-2.79 (m, 1H); 2.31-2.43 (m, 4H); 2.11-2.66 (m, 6H); 1.97-2.07 (m, 2H); 1.83-1.94 (m, 2H).

Workup

  1. stirringThe mixture was stirred at RT for 3 h
  2. stirringThe mixture was stirred at RT for 20 h
  3. dry with materialdried with Na2SO4
  4. customevaporated
  5. customThe residue was purified chromatographically (silica gel 40-63 μm, 5 ml, CCl4/CHCl3 100:0→0:100
  6. dissolutionThe residue was dissolved in ether (1 mL)
  7. addition4N HCl/dioxane (0.10 mL) was added
  8. customthe reaction mixture was evaporated to dryness
  9. customrecrystallized from i-PrOH/Et2O
  10. customThe crystals were separated by filtration

Sources & evidence

ORD record
ord-2cff0e488d8042c2b9cd616ccd20236f
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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