Water → HCID 19955517, compound

HRID 1081666Notes

Reaction equation

HRID 1081666 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][CH2:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17](OS(C(F)(F)F)(=O)=O)=[CH:16][CH:15]=2)[CH3:13])=[C:4]([CH3:28])[N:3]=1.[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[C:34]([F:36])[CH:35]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.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>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][CH2:10][CH2:11][CH:12]([C:14]2[CH:15]=[CH:16][C:17]([C:32]3[CH:31]=[C:30]([F:29])[CH:35]=[C:34]([F:36])[CH:33]=3)=[CH:18][CH:19]=2)[CH3:13])=[C:4]([CH3:28])[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 19955492HCID 19955492, compound

Product 1

HCID 19955517HCID 19955517, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
115 °C

Procedure

A solution of 2.0 grams (0.005 mole) of 2,4-diamino-5-[4-(4-trifluoromethylsulfonyloxyphenyl)pentyl]-6-methylpyrimidine (prepared in Step K of this Example), 2.4 grams (0.01 5 mole) of 3,5-difluorophenylboronic acid, and 0.3 gram (catalyst) of tetrakis(triphenylphosphine)palladium(0) in 90 mL of N,N-dimethylformamide was stirred, and 3.5 grams (0.025 mole) of potassium carbonate was added in one portion. Upon completion of addition, the reaction mixture was warmed slowly to 115 ° C. where it was maintained for about 40 hours. The reaction mixture was cooled and poured into 250 mL of water. The mixture was then extracted with three 150 mL portions of ethyl acetate. The combined extracts were washed with three 150 mL portions of an aqueous 10% lithium chloride solution and dried with sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on neutral alumina (deactivated with 6% wt/wt water), using 2°-10% methanol in methylene chloride as the eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 0.5 gram of 2,4-diamino-5-[4-[4-(3,5-difluorophenyl)phenyl]pentyl]-6-methylpyrimidine, mp 129°-134° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. temperaturewas maintained for about 40 hours
  3. temperatureThe reaction mixture was cooled
  4. extractionThe mixture was then extracted with three 150 mL portions of ethyl acetate
  5. washThe combined extracts were washed with three 150 mL portions of an aqueous 10% lithium chloride solution
  6. dry with materialdried with sodium sulfate
  7. filtrationThe mixture was filtered
  8. concentrationthe filtrate was concentrated under reduced pressure to a residue
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e9928a768724478fb0979fa4f4d788c4
Source dataset
uspto-grants-1996_12
Patent number
US05587379

Reaction notes

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