Imidazole → HCID 59370758, compound

HRID 1873983Notes

Reaction equation

HRID 1873983 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C@@H:9]([OH:39])[CH2:10][N:11]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:12][CH2:13][O:14][C:15]2[CH:23]=[C:22]3[C:18]([C:19]([Cl:31])=[N:20][N:21]3[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[F:8].N1C=CN=C1.Cl[Si:46]([CH2:51][CH3:52])([CH2:49][CH3:50])[CH2:47][CH3:48].C(=O)([O-])O.[Na+]>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([C@@H:9]([O:39][Si:46]([CH2:51][CH3:52])([CH2:49][CH3:50])[CH2:47][CH3:48])[CH2:10][N:11]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:12][CH2:13][O:14][C:15]2[CH:23]=[C:22]3[C:18]([C:19]([Cl:31])=[N:20][N:21]3[C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 13819ChlorotriethylsilaneHCID 516892Sodium BicarbonateHCID 59370724HCID 59370724, compound

Product 1

HCID 59370758HCID 59370758, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-Tert-butyl 6-(2-((2-(3-amino-4-fluorophenyl)-2-hydroxyethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-chloroindazole-1-carboxylate (601.2 mg) which can be prepared according to the method described in Reference example 69, etc. and imidazole (290.3 mg; Tokyo Chemical Industry Co., Ltd) were dissolved in dehydrated DMF (5 mL), added with chlorotriethylsilane (705 μL; manufactured by Shin-Etsu Chemical Co., Ltd.), and then the mixture was stirred for three hours at room temperature. The reaction solution was added to saturated solution of sodium hydrogen carbonate solution and extracted twice with ethyl acetate. The organic layer was washed twice with water and once with brine, dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography (“COLUMN-B”; n-hexane:ethyl acetate=84:16→64:36) to obtain the title compound (480 mg).

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe organic layer was washed twice with water and once with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe resulting residue was purified by column chromatography (“COLUMN-B”; n-hexane:ethyl acetate=84:16→64:36)

Sources & evidence

ORD record
ord-4fe11d80dc734d92ad8ab60752ffd69b
Source dataset
uspto-grants-2012_11
Patent number
US08304443B2

Reaction notes

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