Water → N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

HRID 445924Notes

Reaction equation

HRID 445924 reaction equation
C([O:3][C:4]([C:6]1[C:7]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[N:8][C:9]([N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])=[N:10][C:11]=1[CH:12]([CH3:14])[CH3:13])=O)C.[H-].C([Al+]CC(C)C)C(C)C.O>C1(C)C=CC=CC=1>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:7]2[C:6]([CH2:4][OH:3])=[C:11]([CH:12]([CH3:14])[CH3:13])[N:10]=[C:9]([N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])[N:8]=2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 962WaterHCID 21225700DiisobutylaluminumhydrideHCID 22259911Ethyl 4-(4-fluorophenyl)-2-[(methanesulfonyl)(methyl)amino]-6-(propan-2-yl)pyrimidine-5-carboxylate

Product 1

HCID 9819937N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Ethyl 2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-carboxylic acid (100.0 g) and toluene (500.0 mL) were added to a reactor under nitrogen atmosphere. The reaction mixture was cooled to −78° C. A solution of diisobutylaluminium hydride in toluene (1.5 M, 200.0 mL) was slowly added thereto. The temperature of the reaction mixture was adjusted to 0° C. The reaction mixture was stirred for over 1 hour and then water (500.0 mL) was added thereto. The separated organic layer was sequentially washed with 1N hydrochloric acid solution (500.0 mL), 5% sodium bicarbonate solution (500.0 mL), and then water (500.0 mL), and then concentrated under reduced pressure. n-Hexane (300.0 mL) was added to the resulting residue under stirring. The resulting suspension was filtered under reduced pressure, and then dried to obtain N-[4-(4-fluorophenyl)-5-hydroxymethyl-6-isopropyl-pyrimidin-2-yl]-N-methyl-methanesulfonamide as a white solid (72.3 g, yield 81%).

Workup

  1. customwas adjusted to 0° C
  2. washThe separated organic layer was sequentially washed with 1N hydrochloric acid solution (500.0 mL), 5% sodium bicarbonate solution (500.0 mL)
  3. concentrationwater (500.0 mL), and then concentrated under reduced pressure
  4. additionn-Hexane (300.0 mL) was added to the resulting residue
  5. stirringunder stirring
  6. filtrationThe resulting suspension was filtered under reduced pressure
  7. customdried

Sources & evidence

ORD record
ord-c6ebe5e7a49f486cba92658be847ee56
Source dataset
uspto-grants-2013_07
Patent number
US08476432B2

Reaction notes

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