Picolinic acid → HCID 86635171, compound

HRID 219726Notes

Reaction equation

HRID 219726 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.[C:10]([C:14]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH2:30])[CH2:22][CH2:21]2)[CH:17]=[C:16]([CH:31]2[CH2:34][CH2:33][CH2:32]2)[N:15]=1)([CH3:13])([CH3:12])[CH3:11].C(N(C(C)C)CC)(C)C.OC1C2N=NNC=2C=CC=1.[ClH:54].C(N=C=NCCCN(C)C)C>ClCCl>[ClH:54].[C:10]([C:14]1[N:19]=[C:18]([N:20]2[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[O:9])[CH2:24][CH2:25]2)[CH:17]=[C:16]([CH:31]2[CH2:34][CH2:33][CH2:32]2)[N:15]=1)([CH3:13])([CH3:11])[CH3:12]

Participants

7

Reactant 5

HCID 1018Picolinic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 690260674-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)piperazin-1-yl]-butylamineHCID 178418300HCID 178418300, compound

Product 1

HCID 86635171HCID 86635171, compoundYield 84.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.28 g of picolic acid (2.32 mmol) and 0.8 g of 4-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butylamine (2.32 mmol) were dissolved in 30 ml of dichloromethane. After addition of 1.19 g of diisopropylethylamine (9.26 mmol), 0.155 g of hydroxybenzotriazole (HOBt, 1.15 mmol), and 0.487 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCl, 2.54 mmol) at 0° C., the reaction mixture was stirred for 16 h at room temperature. 0.24 g of N-Ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride were added and the reaction mixture was stirred for 5 h. 100 ml of dichloromethane were added. The organic layer was washed twice with water. The dichlormethane phase was dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using ethyl acetate as eluent. The residue was re-dissolved in 15 ml of diethylether and treated with 1 N hydrochloric acid in diethyl ether. The precipitate was collected by filtration to yield 0.95 g of the title compound as a hydrochloride salt.

Workup

  1. stirringthe reaction mixture was stirred for 5 h
  2. washThe organic layer was washed twice with water
  3. dry with materialThe dichlormethane phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude product was purified by chromatography on silica gel
  7. dissolutionThe residue was re-dissolved in 15 ml of diethylether
  8. additiontreated with 1 N hydrochloric acid in diethyl ether
  9. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-00b5a3093bc24c87b1670aaff1cd2548
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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