1,2-Dimethoxyethane → 1-(2-Cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-4-[(2-cyclopropyl-4-thiazolyl)methoxy]-2(1h)-pyridinone

HRID 2203113Notes

Reaction equation

HRID 2203113 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][N:12]([C:15]3[CH:16]=[CH:17][C:18]4[N:22]=[C:21]([CH:23]5[CH2:25][CH2:24]5)[N:20]([CH3:26])[C:19]=4[CH:27]=3)[C:11](=[O:28])[CH:10]=2)[N:6]=1.[CH:29]1(B(O)O)[CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:23]1([C:21]2[N:20]([CH3:26])[C:19]3[CH:27]=[C:15]([N:12]4[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:5]5[N:6]=[C:2]([CH:29]6[CH2:31][CH2:30]6)[S:3][CH:4]=5)=[CH:10][C:11]4=[O:28])[CH:16]=[CH:17][C:18]=3[N:22]=2)[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 1213862714-[(2-Bromo-4-thiazolyl)methoxy]-1-(2-cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-2(1h)-pyridinone

Product 1

HCID 897026711-(2-Cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-4-[(2-cyclopropyl-4-thiazolyl)methoxy]-2(1h)-pyridinoneYield 24.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
150 °C

Procedure

A mixture of 4-((2-bromo-1,3-thiazol-4-yl)methoxy)-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (54 mg), cyclopropylboronic acid (30.4 mg), tetrakis(triphenylphosphine)palladium (6.8 mg), potassium carbonate (65.3 mg), DME (1.5 ml) and water (0.5 ml) was heated at 150° C. for 20 min under microwave irradiation. The reaction mixture was then cooled to room temperature, poured into water and extracted with EtOAc. The extract was washed with brine, dried over MgSO4, concentrated and purified by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH). The resulting solid was recrystallized from EtOH-water to give the title compound (12.2 mg) as a white solid.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. extractionextracted with EtOAc
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified by silica gel column chromatography (hexane/EtOAc
  7. customThe resulting solid was recrystallized from EtOH-water

Sources & evidence

ORD record
ord-5f03c5b2eb8f4846b2337238d99457e3
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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