Triethylamine → Adamantane-1-carboxylic acid{4,5-dimethyl-3-[2-(2,2,2-trifluoro-ethoxy)-ethyl]-3H-thiazol-2-ylidene}-amide

HRID 255092Notes

Reaction equation

HRID 255092 reaction equation
Br.[CH3:2][C:3]1[N:4]([CH2:10][CH2:11][O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[C:5](=[NH:9])[S:6][C:7]=1[CH3:8].C(N(CC)CC)C.[C:25]12([C:35](Cl)=[O:36])[CH2:34][CH:29]3[CH2:30][CH:31]([CH2:33][CH:27]([CH2:28]3)[CH2:26]1)[CH2:32]2>C1COCC1>[C:13]([O-:36])(=[O:12])[CH3:14].[NH4+:4].[CH3:2][C:3]1[N:4]([CH2:10][CH2:11][O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[C:5](=[N:9][C:35]([C:25]23[CH2:34][CH:29]4[CH2:28][CH:27]([CH2:33][CH:31]([CH2:30]4)[CH2:32]2)[CH2:26]3)=[O:36])[S:6][C:7]=1[CH3:8]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 989151-Adamantanecarbonyl chlorideHCID 668592714,5-dimethyl-3-[2-(2,2,2-trifluoro-ethoxy)-ethyl]-3H-thiazol-2-ylideneamine hydrobromide

Product 2

HCID 517165Ammonium AcetateHCID 66858519Adamantane-1-carboxylic acid{4,5-dimethyl-3-[2-(2,2,2-trifluoro-ethoxy)-ethyl]-3H-thiazol-2-ylidene}-amideYield 6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 85A (0.20 g, 0.8 mmol) in THF (10 mL) was added triethylamine (0.4 mL) and adamantane-1-carbonyl chloride (0.2 g, 1 mmol). The mixture was heated at reflux overnight and then concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with 1M aqueous NaHCO3, dried (Na2SO4), filtered, and concentrated. Purification by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes afforded 10 mg of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.60-1.75 (m, J=28.8 Hz, 6 H), 1.83 (d, J=12.7 Hz, 6 H), 1.93-2.01 (m, 3 H), 2.15 (s, 3 H), 2.20 (s, 3 H), 3.92 (t, J=5.3 Hz, 2 H), 4.09 (q, J=9.5 Hz, 2 H), 4.28 (t, J=5.3 Hz, 2 H); MS (ESI+) m/z 417 (M+H)+; Anal. Calculated for C20H17F3N2O25: C, 57.67; H, 6.53; N, 6.73. Found: C, 57.53; H, 6.55; N, 6.69.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with ethyl acetate
  5. washwashed with 1M aqueous NaHCO3
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size)

Sources & evidence

ORD record
ord-3f0506a1f2904117bd258cad433351d0
Source dataset
uspto-grants-2011_01
Patent number
US07875639B2

Reaction notes

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