3-Fluorobenzoic Acid → HCID 11540003, compound

HRID 219732Notes

Reaction equation

HRID 219732 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=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:5](=[O:7])[C:4]3[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[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 99683-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 11540003HCID 11540003, compoundYield 92.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.29 g of 3-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. Addition of 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) at 0° C. was followed by stirring the reaction mixture for 16 h at room temperature. 30 ml of dichloromethane were added, the organic layer was washed with aqueous saturated sodium chloride. The aqueous phase was re-extracted once with dichloromethane. 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 (15:1). Fractions containing the product were combined, the solvent was evaporated to yield 0.88 g of the title compound as a white solid.

Workup

  1. washthe organic layer was washed with aqueous saturated sodium chloride
  2. extractionThe aqueous phase was 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-ddb764dd41f54413b4f2d2e82f327123
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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