Ammonia → 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxamide

HRID 2391664Notes

Reaction equation

HRID 2391664 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([O:26]C)=O)=[C:21]([O:28][C@@H:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[C:37]([F:40])([F:39])[F:38])[CH3:30])[CH:20]=3)[C:12]=2[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH3:41]>CO>[Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([NH2:41])=[O:26])=[C:21]([O:28][C@@H:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[C:37]([F:39])([F:38])[F:40])[CH3:30])[CH:20]=3)[C:12]=2[CH:11]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 68767242Methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxylate

Product 1

HCID 687681345-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 5.1 g of methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}thio-phene-2-carboxylate and 500 ml of a 7 N solution of ammonia in methanol is stirred in an autoclave at 125° C. for 4 hours. The mixture is allowed to cool down to room temperature and concentrated to dryness. During the reaction the TBDMS group of the title product is partially removed. The crude is purified by flash chromatography [silica gel, eluent: cyclohexane/ethyl acetate/methanol, elution gradient of 40/60/0 (v/v/v) to 0/100/0 (v/v/v) and then to 0/90/10 (v/v)] to give the title compound. Additionally, 5-[6-(hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxamide is obtained.

Workup

  1. temperatureto cool down to room temperature
  2. concentrationconcentrated to dryness
  3. customDuring the reaction the TBDMS group of the title product
  4. customis partially removed
  5. customThe crude is purified by flash chromatography [silica gel, eluent
  6. washcyclohexane/ethyl acetate/methanol, elution gradient of 40/60/0 (v/v/v) to 0/100/0 (v/v/v)

Sources & evidence

ORD record
ord-4ff337ec4e334da59203733ef091870d
Source dataset
uspto-grants-2012_09
Patent number
US08273890B2

Reaction notes

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