Triethylamine → (3-{[(3,5-Dimethyl-isoxazole-4-sulfonyl)-(4-pyrimidin-2-yl-benzyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester

HRID 2117568Notes

Reaction equation

HRID 2117568 reaction equation
[C:1]([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[N:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[CH:20][CH:19]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:38][C:39]1[C:43]([S:44](Cl)(=[O:46])=[O:45])=[C:42]([CH3:48])[O:41][N:40]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([S:44]([C:43]2[C:39]([CH3:38])=[N:40][O:41][C:42]=2[CH3:48])(=[O:46])=[O:45])[CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[N:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[CH:22][CH:23]=2)[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 27363193,5-Dimethylisoxazole-4-sulfonyl chloride2×HCID 18376223{3-[(4-Pyrimidin-2-yl-benzylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester

Product 1

HCID 53857383(3-{[(3,5-Dimethyl-isoxazole-4-sulfonyl)-(4-pyrimidin-2-yl-benzyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl esterYield 52.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {3-[(4-pyrimidin-2-yl-benzylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester (83.3 mg, 0.2054 mmol), prepared in Step A of Example 130, in CH2Cl2 was added triethylamine (0.94 mL, 0.68 mmol) and 3,5-dimethyl-isoxazole-4-sulfonyl chloride (44.2 mg, 0.226 mmol) and the reaction was heated at reflux overnight. After cooling to room temperature, additional triethylamine (0.94 mL) and 3,5-dimethyl-isoxazole-4-sulfonyl chloride (44 mg) was added. The reaction was heated at reflux for 72 h and was cooled to room temperature. The organic solution was washed sequentially with 5.5% aqueous HCl, water, saturated sodium bicarbonate solution, and brine. The organic solution was dried (MgSO4), filtered, and concentrated. Flash chromatography (CHCl3:MeOH 99:1) provided the title compound of Step A (61 mg). MS 565 (M+1).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux overnight
  3. temperatureThe reaction was heated
  4. temperatureat reflux for 72 h
  5. temperaturewas cooled to room temperature
  6. washThe organic solution was washed sequentially with 5.5% aqueous HCl, water, saturated sodium bicarbonate solution, and brine
  7. dry with materialThe organic solution was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c94446beb3ca4a31b4c85b97f44b7934
Source dataset
uspto-grants-2008_10
Patent number
US07442702B2

Reaction notes

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