1,2-Dimethoxyethane → HCID 59379932, compound

HRID 2353755Notes

Reaction equation

HRID 2353755 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[CH:5]=[C:4]([C:15]([S:18]([C:21]2[S:22][CH:23]=[C:24]([CH3:26])[N:25]=2)(=[O:20])=[O:19])([CH3:17])[CH3:16])[N:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>CN(C=O)C.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.O.C(O)C>[CH3:14][C@H:9]1[CH2:10][O:11][CH2:12][CH2:13][N:8]1[C:6]1[CH:5]=[C:4]([C:15]([S:18]([C:21]2[S:22][CH:23]=[C:24]([CH3:26])[N:25]=2)(=[O:20])=[O:19])([CH3:17])[CH3:16])[N:3]=[C:2]([C:35]2[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=2)[N:7]=1

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 59380091HCID 59380091, compound

Product 1

HCID 59379932HCID 59379932, compoundYield 67.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine (480 mg, 1.15 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (378 mg, 1.73 mmol) and 2M aqueous sodium carbonate solution (2.8 mL, 5.60 mmol) in a mixture of DMF (2 mL), 1,2-dimethoxyethane (2 mL), ethanol (2 mL) and water (5 mL) was purged with nitrogen for 10 minutes prior to addition of bis(triphenylphosphine)palladium(II) chloride (54 mg, 0.08 mmol). The reaction mixture was heated to 85° C. and stirred at that temperature, under nitrogen for 3 hours. The reaction mixture was then cooled and partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (25 mL). Combined organic layers were washed with brine (50 mL), dried (MgSO4), filtered and evaporated to afford the crude product, which was purified by flash silica chromatography, elution gradient 25 to 75% ethyl acetate in isohexane, to give the desired material (367 mg).

Workup

  1. customwas purged with nitrogen for 10 minutes
  2. temperatureThe reaction mixture was then cooled
  3. custompartitioned between ethyl acetate (50 mL) and water (30 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer re-extracted with ethyl acetate (25 mL)
  6. washCombined organic layers were washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customto afford the crude product, which
  11. customwas purified by flash silica chromatography, elution gradient 25 to 75% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-739b1174e9d74ee98ba1c90a2c008505
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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