Sodium hydride → HCID 15790377, compound

HRID 1608792Notes

Reaction equation

HRID 1608792 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[C:13]#[N:14])=[CH:6][CH:5]=1.Br[C:23]1[CH:24]=[N:25][CH:26]=[N:27][CH:28]=1>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])([C:23]2[CH:24]=[N:25][CH:26]=[N:27][CH:28]=2)[C:13]#[N:14])=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 783445-BromopyrimidineHCID 15790376HCID 15790376, compound

Product 1

HCID 15790377HCID 15790377, compoundYield 97.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
50 °C

Procedure

A 1 L 4-neck flask under a nitrogen atmosphere was charged with 4.4 g. of 60% sodium hydride (1.1 equiv., 0.11 moles), and washed with hexanes, in 75 ml. DMF. Then over 30 minutes, 27.3 g. of 4-(4-chlorophenyl)-2-(2-fluorophenyl) butanenitrile (1.0 equiv., 0.10 moles) in 110 ml. DMF was added dropwise to the base causing an exotherm to 30° C. After the addition was complete, the reaction mixture was stirred for 30 minutes. Over 5 minutes 17.5 g. of 5-bromopyrimidine (1.1 equiv., 0.11 moles) in 75 mi. DMF was added to the reaction mixture which was heated at 50° C. and monitored by GLC analysis. The reaction was quenched after 2 hours by the addition of 350 ml. water and extracted with 600 ml. ethyl acetate. The organic phase was washed with three 300 ml. portions of water, the organic phase dried over anhydrous magnesium sulfate, and then concentrated in vacuo at 50° C. to give 34.2 grams oil which solidified. The solid was with triturated with 75 ml. isopropanol, filtered, and dried to give 16.5 g. white solid (47.0% yield), m.p.=86° C.-88° C.

Workup

  1. additionA 1 L 4-neck flask under a nitrogen atmosphere was charged with 4.4 g
  2. customto 30° C
  3. additionAfter the addition
  4. waitOver 5 minutes 17.5 g
  5. customThe reaction was quenched after 2 hours by the addition of 350 ml
  6. extractionwater and extracted with 600 ml
  7. washThe organic phase was washed with three 300 ml
  8. dry with materialportions of water, the organic phase dried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo at 50° C.

Sources & evidence

ORD record
ord-c7466c87e61d435e8b7405a05395691a
Source dataset
uspto-grants-1995_03
Patent number
US05397793

Reaction notes

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