Water → (R)-3-[3-(4,6-Dimethyl-benzo[d]isothiazol-3-ylmethyl)-2-oxo-2,3-dihydro-imidazo[4,5-c]pyridin-1-yl]-3-phenyl-propionic acid ethyl ester

HRID 2175181Notes

Reaction equation

HRID 2175181 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C@@H:6]([NH:13][C:14]1[C:19]([N+:20]([O-])=O)=[CH:18][CH:17]=[C:16]([CH3:23])[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].Br[CH2:26][C:27]1[C:31]2[C:32]([CH3:37])=[CH:33][C:34]([CH3:36])=[CH:35][C:30]=2[S:29][N:28]=1.C([O-])([O-])=[O:39].[K+].[K+].O>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C@@H:6]([N:13]1[C:17]2[CH:18]=[CH:19][N:20]=[CH:23][C:16]=2[N:15]([CH2:26][C:27]2[C:31]3[C:32]([CH3:37])=[CH:33][C:34]([CH3:36])=[CH:35][C:30]=3[S:29][N:28]=2)[C:14]1=[O:39])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 584973913-Bromomethyl-4,6-dimethyl-benzo[d]isothiazoleHCID 58497430(R)-3-(6-Methyl-3-nitro-pyridin-2-ylamino)-3-phenyl-propionic acid ethyl ester

Product 1

HCID 58497400(R)-3-[3-(4,6-Dimethyl-benzo[d]isothiazol-3-ylmethyl)-2-oxo-2,3-dihydro-imidazo[4,5-c]pyridin-1-yl]-3-phenyl-propionic acid ethyl esterYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-3-(2-oxo-2,3-dihydro-imidazo[4,5-c]pyridin-1-yl)-3-phenyl-propionic acid ethyl ester (refer to example 2) (50 mg, 0.16 mmol) in DMF (10 mL) were added 3-Bromomethyl-4,6-dimethyl-benzo[d]isothiazol (62 mg, 0.24 mmol) and K2CO3 (44 mg, 0.32 mmol) at room temperature under nitrogen atmosphere. The solution was heated to 100° C. for 2 hours. The solution was cooled and water was added. The solution was extracted with EtOAc and the combined organic layer was dried with MgSO4. The solution was filtered and concentrated. The residue was purified by silica gel flash column chromatography with 20% EtOAc in Hexane as the eluent to afford the title compound (15 mg, 90%) as colorless foam.

Workup

  1. temperatureThe solution was cooled
  2. extractionThe solution was extracted with EtOAc
  3. dry with materialthe combined organic layer was dried with MgSO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography with 20% EtOAc in Hexane as the eluent

Sources & evidence

ORD record
ord-e2ef67f18b3f45919256e7c866c12086
Source dataset
uspto-grants-2015_06
Patent number
US09062056B2

Reaction notes

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