Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-(3-tert-butyl-isoxazol-5-yl)-7-chloro-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine

HRID 570214Notes

Reaction equation

HRID 570214 reaction equation
[NH2:1][C:2]1[C:3]([NH:19][C:20]([C:22]2[O:26][N:25]=[C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:23]=2)=O)=[N:4][C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]=1[Cl:8].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>O1CCOCC1.CCOC(C)=O>[C:27]([C:24]1[CH:23]=[C:22]([C:20]2[NH:1][C:2]3[C:3]([N:19]=2)=[N:4][C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]=3[Cl:8])[O:26][N:25]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 674111003-Tert-butyl-isoxazole-5-carboxylic acid [3-amino-4-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

Product 1

HCID 1360731722-(3-tert-butyl-isoxazol-5-yl)-7-chloro-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-tert-butyl-isoxazole-5-carboxylic acid [3-amino-4-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide (36.2 mg, 0.0825 mmol, prepared as described in STEP B above) in 1,4-dioxane (10 mL) was treated with (+)-10-camphorsulfonic acid (38.3 mg, 0.165 mmol), and the mixture was heated to 100° C. for 5 h. The cooled mixture was diluted with EtOAc (20 mL) and washed with saturated aqueous NaHCO3 (20 mL). The organic extract was dried over MgSO4 and concentrated in vacuo. The residue was purified on an 8-g SEPRA Si 35 SPE column (Flow rate=15 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:3 over 40 min) to yield 2-(3-tert-butyl-isoxazol-5-yl)-7-chloro-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine as a white solid. 1H-NMR (400 MHz, CDCl3) δ: 7.77 (d, J=7.8 Hz, 1H), 7.58-7.64 (m, 1H), 7.50-7.58 (m, 2H), 7.49 (s, 1H), 7.16 (s, 1H), 1.88 (br. s., 1H), 1.39 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C20H16N4OClF3: 421.1 (M+H); Measured: 421.1.

Workup

  1. washwashed with saturated aqueous NaHCO3 (20 mL)
  2. extractionThe organic extract
  3. dry with materialwas dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on an 8-g SEPRA Si 35 SPE column (Flow rate=15 mL/min

Sources & evidence

ORD record
ord-bb70ee5f9cf14585b76c41b623c9ec55
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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