4-Toluenesulfonyl chloride → 2-Amino-6-(5-methylfuran-2-yl)-5-nitropyrimidin-4-yl 4-methylbenzenesulfonate

HRID 876953Notes

Reaction equation

HRID 876953 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([N+:9]([O-:11])=[O:10])=[C:4]([C:12]2[O:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:3]=1.C(N(CC)CC)C.[C:25]1([CH3:35])[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1.CCCC(C)C>C(#N)C.ClCCl.C1(C)C=CC=CC=1.CCOC(C)=O>[CH3:17][C:14]1[O:13][C:12]([C:4]2[C:5]([N+:9]([O-:11])=[O:10])=[C:6]([O:8][S:31]([C:28]3[CH:29]=[CH:30][C:25]([CH3:35])=[CH:26][CH:27]=3)(=[O:33])=[O:32])[N:7]=[C:2]([NH2:1])[N:3]=2)=[CH:16][CH:15]=1

Participants

9

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 78922-MethylpentaneHCID 8471Triethylamine2×HCID 178423996HCID 178423996, compound

Product 1

HCID 866553142-Amino-6-(5-methylfuran-2-yl)-5-nitropyrimidin-4-yl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A stirred suspension of 2-amino-6-(5-methyl-2-furyl)-5-nitro-4-pyrimidinol (12) (20.96 g, 0.089 mol) in dry acetonitrile (800 mL, 40 volumes) in a flame-dried three-necked flask at 22° C. was treated with triethylamine (27.24 mL, 0.196 mol, 2.2 eq). The resulting triethylamine salt was clearly insoluble in the reaction solvent, a thick yellow precipitate becoming apparent. The mixture was heated to a temperature of 50° C. and treated portionwise with para-toluenesulfonyl chloride (18.57 g, 0.097 mol, 1.1 eq). The yellow precipitate was rapidly replaced by a dark orange/brown solution. Stirring at 50° C. was continued for a further 3.5 hr, after which time LC-MS and TLC (1:1 EtOAc:iso-hexane) analysis indicated a complete reaction. The reaction mixture was cooled to 22° C. and reduced in vacuo to yield a light brown solid. This was dissolved in dichloromethane (800 mL, 40 volumes) and washed twice with 1.2-M aqueous hydrochloric acid. The organic fraction was dried over magnesium sulfate and reduced in vacuo to yield a cream coloured solid. Trituration with toluene was effective in removing excess tosyl chloride to give the required tosylate product (compound 13) as an off-white solid. Drying at 40° C. left 22.33 g (65% yield).

Workup

  1. customa complete reaction
  2. temperatureThe reaction mixture was cooled to 22° C.
  3. customto yield a light brown solid
  4. washwashed twice with 1.2-M aqueous hydrochloric acid
  5. dry with materialThe organic fraction was dried over magnesium sulfate
  6. customto yield a cream
  7. customin removing excess tosyl chloride

Sources & evidence

ORD record
ord-9309f88288c846d38ff21d274e46bd37
Source dataset
uspto-grants-2015_03
Patent number
US08987279B2

Reaction notes

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