Tetrabutylammonium Fluoride → 6-(4-Ethynyl-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 217084Notes

Reaction equation

HRID 217084 reaction equation
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:17]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[C:26][Si](C)(C)C)=[CH:21][C:20]=3[CH3:31])=[C:16]([F:32])[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.O>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:17]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[CH:26])=[CH:21][C:20]=3[CH3:31])=[C:16]([F:32])[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 865905277-Fluoro-6-(2-methyl-4-trimethylsilanylethynyl-phenylamino)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxyamide

Product 1

HCID 588906896-(4-Ethynyl-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideYield 66.1%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

7-Fluoro-6-(2-methyl-4-trimethylsilanylethynyl-phenylamino)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide 11bbb (0.020 g, 0.044 mmol) is dissolved in tetrahydrofuran (0.50 mL) and the reaction solution is cooled to 0° C. TBAF (50 uL, 0.050 mmol, 1 M solution in tetrahydrofuran) is added. The reaction mixture is warmed to room temperature and additional TBAF (25 uL, 0.025 mmol, 1 M solution in tetrahydrofuran) is added. The reaction mixture is stirred at 50° C. for 2 hours under N2. The reaction mixture is cooled to room temperature, a few drops of H2O are added and then it is concentrated under reduced pressure. The residue is purified by FCC (eluting with 20:1 methylene chloride:methanol) to yield 0.011 g (65%) of the pure desired product. MS APCI (−) m/z 377 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.56 (broad s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.28 (s, 1H), 7.11 (d, 1H), 6.42 (broad, 1H), 3.70 (br s, 2H), 2.96 (d, 1H), 2.37 (s, 3H), 0.85 (m, 1H), 0.50 (m, 2H), 0.22 (m, 2H).

Workup

  1. temperatureThe reaction mixture is warmed to room temperature
  2. temperatureThe reaction mixture is cooled to room temperature
  3. concentrationit is concentrated under reduced pressure
  4. customThe residue is purified by FCC (eluting with 20:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-9aee00763fa24096a9f2022097950b25
Source dataset
uspto-grants-2012_06
Patent number
US08193231B2

Reaction notes

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