Triethylamine → HCID 178434756, compound

HRID 1159399Notes

Reaction equation

HRID 1159399 reaction equation
[F:1][C:2]1[C:15]([CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:14][CH:13]=[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.[CH3:29][C:30]1[C:34]([C:35]([Cl:37])=[O:36])=[C:33]([CH3:38])[O:32][N:31]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[ClH:37].[F:1][C:2]1[C:15]([CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:14][CH:13]=[CH:12][C:3]=1[O:4][C@H:5]1[CH2:8][C@H:7]([CH2:9][N:10]([CH3:11])[C:35]([C:34]2[C:30]([CH3:29])=[N:31][O:32][C:33]=2[CH3:38])=[O:36])[CH2:6]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27362653,5-Dimethylisoxazole-4-carbonyl ChlorideHCID 178484140HCID 178484140, compound

Product 1

HCID 178434756HCID 178434756, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Example 391, ({trans-3-[2-fluoro-3-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl)methylamine (200 mg, 0.7 mmol) and triethylamine (0.1 mL, 0.7 mmol) were dissolved in CH2Cl2 (2 mL). 3,5-Dimethylisoxazole-4-carbonyl chloride (109 mg, 0.7 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, 3 g, hexane/CHCl3 20:80→0:100, then CHCl3/MeOH 100:0→95:5). The residue was dissolved in ether (1 mL). 4N HCl/dioxane (0.20 mL) was added, and the reaction mixture was evaporated to dryness. The obtained crystals were washed with ether and dried in vacuo to give the title compound (160 mg, 52%) as yellow crystals. LC/MS data: 416.2 (M+H) (calculated for C23H30FN3O3 415.51). 1H NMR-data (DMSO-d6): 10.64 (br.s, 1H, NH+); 7.13-7.29 (m, 2H, Ar—H); 6.87-7.12 (m, 1H, Ar—H); 4.53-5.07 (m, 1H), 4.38 (br.s, 2H); 3.57-3.67 (m, 1H); 3.37-3.52 (m, 3H); 2.97-3.13 (m, 2H); 2.91 (s, 3H); 2.61-2.78 (m, 1H); 2.28-2.41 (m, 4H); 2.11-2.23 (m, 6H); 1.94-2.06 (m, 2H); 1.79-1.94 (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, 3 g, hexane/CHCl3 20:80→0:100
  6. dissolutionThe residue was dissolved in ether (1 mL)
  7. addition4N HCl/dioxane (0.20 mL) was added
  8. customthe reaction mixture was evaporated to dryness
  9. washThe obtained crystals were washed with ether
  10. customdried in vacuo

Sources & evidence

ORD record
ord-616b95118b5a4106b0c76dd900631268
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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