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

HRID 219733Notes

Reaction equation

HRID 219733 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.C(N(CC)CC)C.OC1C2N=NNC=2C=CC=1.[ClH:28].[C:29]([C:33]1[N:38]=[C:37]([N:39]2[CH2:44][CH2:43][N:42]([CH2:45][CH2:46][CH2:47][CH2:48][NH:49][CH3:50])[CH2:41][CH2:40]2)[CH:36]=[C:35]([CH:51]2[CH2:54][CH2:53][CH2:52]2)[N:34]=1)([CH3:32])([CH3:31])[CH3:30].Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[ClH:28].[C:29]([C:33]1[N:38]=[C:37]([N:39]2[CH2:40][CH2:41][N:42]([CH2:45][CH2:46][CH2:47][CH2:48][N:49]([CH3:50])[C:6](=[O:8])[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)[CH2:43][CH2:44]2)[CH:36]=[C:35]([CH:51]2[CH2:54][CH2:53][CH2:52]2)[N:34]=1)([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 99734-Fluorobenzoic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69028787{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-methyl-amine hydrochlorideHCID 178418300HCID 178418300, compound

Product 1

HCID 69028509N-{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-4-fluoro-N-methyl-benzamide hydrochlorideYield 41.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.5 g of 4-fluorobenzoic acid (3.57 mmol) and 1.27 g of triethylamine (12.57 mmol) were dissolved in 40 ml of dimethylformamide. 0.5 g of hydroxybenzotriazole (HOBt, 3.7 mmol), 1.3 g of {4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-methyl-amine hydrochloride (2.77 mmol), and 0.75 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCl, 3.91 mmol) were added at room temperature, and the reaction mixture was stirred for 16 h. The reaction mixture was partitioned between water and ethyl acetate, the organic phase dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using dichloromethane-methanol (2%). The residue was re-dissolved in isopropanol, treated with 4 N hydrochloric acid in dioxan. The precipitate was collected by filtration and dried to yield 0.6 g of the title compound as a white solid.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. dry with materialthe organic phase dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe crude product was purified by chromatography on silica gel
  6. dissolutionThe residue was re-dissolved in isopropanol
  7. additiontreated with 4 N hydrochloric acid in dioxan
  8. filtrationThe precipitate was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-8daebbd50a234604a633afd9a0485b3e
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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