Isonicotinic Acid → N-{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-isonicotinamide hydrochloride

HRID 219724Notes

Reaction equation

HRID 219724 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.OC1C2N=NNC=2C=CC=1.[C:27]([C:31]1[N:36]=[C:35]([N:37]2[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45][CH2:46][NH2:47])[CH2:39][CH2:38]2)[CH:34]=[C:33]([CH:48]2[CH2:51][CH2:50][CH2:49]2)[N:32]=1)([CH3:30])([CH3:29])[CH3:28].[ClH:52].C(N=C=NCCCN(C)C)C>CN(C)C=O>[ClH:52].[C:27]([C:31]1[N:36]=[C:35]([N:37]2[CH2:38][CH2:39][N:40]([CH2:43][CH2:44][CH2:45][CH2:46][NH:47][C:1](=[O:9])[C:2]3[CH:3]=[CH:4][N:5]=[CH:6][CH:7]=3)[CH2:41][CH2:42]2)[CH:34]=[C:33]([CH:48]2[CH2:51][CH2:50][CH2:49]2)[N:32]=1)([CH3:30])([CH3:28])[CH3:29]

Participants

7

Reactant 5

HCID 5922Isonicotinic AcidHCID 8471TriethylamineHCID 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 69078470N-{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-isonicotinamide hydrochlorideYield 72.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.35 g of isonicotinic acid (2.84 mmol) and 0.87 g of triethylamine (8.62 mmol) were dissolved in 30 ml of dimethylformamide. 0.45 g of hydroxybenzotriazole (HOBt, 3.33 mmol), 1.1 g of 4-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butylamine (3.18 mmol), and 0.6 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCl, 3.13 mmol) were added at room temperature, and the reaction mixture was stirred for 16 h. The reaction mixture was then partitioned between water and ethyl acetate. The organic phase was dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using dichloromethane-methanol (2-10%). The oily residue was re-dissolved in isopropanol, and 1 N hydrochloric acid in diisopropyl ether was added. The mixture was slowly evaporated to yield 1.0 g of the title compound as a yellowish foam.

Workup

  1. customThe reaction mixture was then partitioned between water and ethyl acetate
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe crude product was purified by chromatography on silica gel
  6. dissolutionThe oily residue was re-dissolved in isopropanol
  7. addition1 N hydrochloric acid in diisopropyl ether was added
  8. customThe mixture was slowly evaporated

Sources & evidence

ORD record
ord-9e0c1c1f13a546c3bc9d5facee701f9b
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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