Methyl iodide → 5-(4-fluorophenyl)-3-methyl-2-methylthio-6-(4-pyridyl)-4(3H)-pyrimidinone

HRID 897391Notes

Reaction equation

HRID 897391 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11]CC)=O)=[CH:4][CH:3]=1.[C:14]([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)#[N:15].C(O[K])(C)(C)C.CC(O)(C)C.[CH3:33][N:34]=[C:35]=[S:36].[CH3:37]I>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9](=[O:11])[N:34]([CH3:33])[C:35]([S:36][CH3:37])=[N:15][C:14]=2[C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 75064-CyanopyridineHCID 11167Methyl isothiocyanateHCID 3013910Benzeneacetic acid, 4-fluoro-, ethyl esterHCID 178450467HCID 178450467, compound

Product 1

HCID 223466205-(4-fluorophenyl)-3-methyl-2-methylthio-6-(4-pyridyl)-4(3H)-pyrimidinone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of ethyl 2-(4-fluorophenyl)acetate (273 g, 1.5 mol) and 4-cyanopyridine (156.1 g, 1.5 mol) was dissolved in 1.5 L of DMF in a 12 L, 3-necked r.b.flask equipped with a mechanical stir, temperature probe and 1 L addition funnel. 1.5 L of 1.0M tBuOK/tBuOH (1.5 mol) was added into the solution slowly at RT through a 1L addition funnel. The resulting brown solution was stirred at RT for 1 h. A solution of 109.7 g of MeNCS (1.5 mol) in 750 ml DMF was added into the reaction solution slowly at RT. The temperature of the solution was increased from 26° C. to 33° C. The resulting brown solution was stirred for 1 h. The reaction solution was cooled down to ca. 0° C. using ice-water bath and 93 ml of MeI (1.5 mol) was added into the reaction solution through a 125-ml addition funnel. The reaction solution was stirred at RT and a precipitate formed after 30 min. The suspension was stirred at RT overnight. The solid was filtered off and washed with water (2×200 ml) and dried under vacuum at 50° C. overnight. 5-(4-fluorophenyl)-3-methyl-2-methylthio-6-(4-pyridyl)-3H-pyrimidin-4-one was obtained; MS: m/z (M+H)+ 328; C17H14FN3OS requir. 327.

Workup

  1. customequipped with a mechanical stir, temperature probe and 1 L addition funnel
  2. temperatureThe temperature of the solution was increased from 26° C. to 33° C
  3. stirringThe resulting brown solution was stirred for 1 h
  4. temperatureThe reaction solution was cooled down to ca. 0° C.
  5. stirringThe reaction solution was stirred at RT
  6. customa precipitate formed after 30 min
  7. stirringThe suspension was stirred at RT overnight
  8. filtrationThe solid was filtered off
  9. washwashed with water (2×200 ml)
  10. customdried under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-fa5ce7e66cd74f9d9387b34d61b2c5aa
Source dataset
uspto-grants-2005_07
Patent number
US06921762B2

Reaction notes

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