2-Fluorobenzoic acid → N-{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-2-fluoro-benzamide

HRID 219731Notes

Reaction equation

HRID 219731 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[C:11]([C:15]1[N:20]=[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][NH2:31])[CH2:23][CH2:22]2)[CH:18]=[C:17]([CH:32]2[CH2:35][CH2:34][CH2:33]2)[N:16]=1)([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[C:11]([C:15]1[N:20]=[C:19]([N:21]2[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=3[F:1])[CH2:25][CH2:26]2)[CH:18]=[C:17]([CH:32]2[CH2:35][CH2:34][CH2:33]2)[N:16]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 5

HCID 99352-Fluorobenzoic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 690260674-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)piperazin-1-yl]-butylamineHCID 178418300HCID 178418300, compound

Product 1

HCID 11719690N-{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-2-fluoro-benzamideYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.29 g of 2-fluoro-benzoic acid (2.03 mmol) and 0.7 g of 4-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butylamine (2.03 mmol) were dissolved in 25 ml of dichloromethane. 1.04 g of diisopropylethylamine (8.04 mmol), 0.19 g of hydroxybenzotriazole (HOBt, 1.4 mmol), and 0.46 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCl, 2.4 mmol) were added at 0° C. and the reaction mixture was stirred for 16 h at room temperature. 25 ml of dichloromethane were added, the organic layer washed with aqueous saturated sodium chloride, the aqueous phase re-extracted once with dichloromethane, and the combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using ethyl acetate and ethyl acetate-methanol (5%). Fractions containing the product were combined. The solvent was evaporated to yield 0.84 g of the title compound as a white solid.

Workup

  1. washthe organic layer washed with aqueous saturated sodium chloride
  2. extractionthe aqueous phase re-extracted once with dichloromethane
  3. dry with materialthe combined organic phases were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude product was purified by chromatography on silica gel
  7. additionFractions containing the product
  8. customThe solvent was evaporated

Sources & evidence

ORD record
ord-aa2d20f9fd6c455fa94a422eafb9782a
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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