Ethanol → HCID 57504924, compound

HRID 2060798Notes

Reaction equation

HRID 2060798 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:9]23[CH2:17][C@H:16]([OH:18])[CH2:15][C@H:14]2[CH2:13][S:12][C:11]([NH:19][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:10]3)[CH:5]=[CH:6][C:7]=1[F:8].C(O)C.[N:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C@:9]23[CH2:17][C@H:16]([OH:18])[CH2:15][C@H:14]2[CH2:13][S:12][C:11]([NH:19][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:10]3)=[CH:3][C:2]=1[C:35]1[CH:36]=[N:31][CH:32]=[N:33][CH:34]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 57504923HCID 57504923, compound

Product 1

HCID 57504924HCID 57504924, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
97 °C

Procedure

A solution of N-((4aR,6R,7aS)-7a-(3-bromo-4-fluorophenyl)-6-hydroxy-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl)benzamide (0.588 g, 1.31 mmol) in a mixture of 1,2-dimethoxyethane (8 mL), ethanol (4 mL) and water (4 mL) is purged with nitrogen and is heated to 97° C. Pyrimidine-5-boronic acid (0.810 g, 6.54 mmol), cesium carbonate (2.56 g, 7.84 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.184 g, 0.261 mmol) is added in a single portion and the reaction is heated at 97° C. for 30 minutes. The reaction is cooled, diluted with water and is extracted twice with ethyl acetate. The organic layer is dried over sodium sulfate and the crude product is purified by silica gel chromatography with a linear gradient of 0% to 40% ethyl acetate in dichloromethane over 20 minutes to give the title compound (0.464 g, 79%). ES/MS m/e: 449 (M+1).

Workup

  1. customis purged with nitrogen
  2. temperaturethe reaction is heated at 97° C. for 30 minutes
  3. temperatureThe reaction is cooled
  4. extractionis extracted twice with ethyl acetate
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. customthe crude product is purified by silica gel chromatography with a linear gradient of 0% to 40% ethyl acetate in dichloromethane over 20 minutes

Sources & evidence

ORD record
ord-1caba26cc8e3473b83bd0dfb1a2fbc39
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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