Methylamine → Benzenesulfonamide, 4-(2-amino-5-pyrimidinyl)-2-fluoro-N-methyl-

HRID 500269Notes

Reaction equation

HRID 500269 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[C:4]([F:12])[CH:3]=1.CN.[CH2:15]([N:17](CC)CC)C.CC1(C)C(C)(C)OB([C:30]2[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=2)O1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.O.C1(C)C=CC=CC=1.C(O)C.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.CCOCC>[NH2:36][C:33]1[N:32]=[CH:31][C:30]([C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH:17][CH3:15])(=[O:10])=[O:9])=[C:4]([F:12])[CH:3]=2)=[CH:35][N:34]=1

Participants

12

Reactant 5

HCID 6329MethylamineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27363104-Bromo-2-fluorobenzene-1-sulfonyl chlorideHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol ester

Product 1

HCID 67225169Benzenesulfonamide, 4-(2-amino-5-pyrimidinyl)-2-fluoro-N-methyl-Yield 84.6%

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

4-Bromo-2-fluorobenzenesulfonyl chloride (100 mg, 0.36 mmol) was added to a mixture of methylamine (2M in THF, 0.275 mL, 0.55 mmol) and triethylamine (0.10 mL, 0.73 mmol) in methylene chloride (2.0 mL). The reaction mixture was quenched with saturated NaHCO3 (1.0 mL) and concentrated to afford the crude intermediate in water. A mixture of the intermediate in water, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (81 mg, 0.36 mmol), tetrakis(triphenylphosphine)palladium (20 mg, 0.02 mmol), potassium carbonate (150 mg, 1.1 mmol) in toluene (2.0 mL) and ethanol (1.0 mL) was heated at 110° C. for 2 h. After cooling to RT, ether was added to the mixture and the solid was filtered, washed with water and ether to afford the desired product (0.086 g, 83%). LCMS: (M+H)=282.9.

Workup

  1. customThe reaction mixture was quenched with saturated NaHCO3 (1.0 mL)
  2. concentrationconcentrated
  3. customto afford the crude intermediate in water
  4. filtrationthe solid was filtered
  5. washwashed with water and ether

Sources & evidence

ORD record
ord-4fadf6f84e47405cb4b56c44ff8d3ccb
Source dataset
uspto-grants-2010_08
Patent number
US07767675B2

Reaction notes

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