Triethylamine → HCID 18362828, compound

HRID 381380Notes

Reaction equation

HRID 381380 reaction equation
C(N(CC)CC)C.[CH:8]([NH:11][C:12]1[C:13]([N:18]2[CH2:23][CH2:22][N:21]([C:24]([C:26]3[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][N:27]=3)=[O:25])[CH2:20][CH2:19]2)=[N:14][CH:15]=[CH:16][CH:17]=1)([CH3:10])[CH3:9].C(Cl)(=O)C(C)(C)C.[NH2:42][C:43]1[CH:47]=[C:46]([CH3:48])[NH:45][N:44]=1>C(Cl)Cl>[CH:8]([NH:11][C:12]1[C:13]([N:18]2[CH2:23][CH2:22][N:21]([C:24]([C:26]3[CH:34]=[CH:33][C:29]([C:30]([NH:42][C:43]4[CH:47]=[C:46]([CH3:48])[NH:45][N:44]=4)=[O:32])=[CH:28][N:27]=3)=[O:25])[CH2:20][CH2:19]2)=[N:14][CH:15]=[CH:16][CH:17]=1)([CH3:9])[CH3:10]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 183628186-[1-[3-(Isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]nicotinic acid

Product 1

HCID 18362828HCID 18362828, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

Triethylamine (0.8 ml) was added to 6-[1-[3-(isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]nicotinic acid (2 g) in methylene chloride (30 ml) for dissolution and cooled. With the slow addition of pivaloyl chloride (0.7 ml) at 0° C.˜5° C., the mixture was stirred at 5° C. for 1 hour. With the addition of triethylamine (0.9 ml) and 3-amino-5-methylpyrazole (0.56 g), the mixture was stirred at 5° C.˜10° C. for 3 hours. The solution was slowly heated and stirred at 15° C.˜20° C. for 30 minutes. The solution was washed with an aqueous sodium bicarbonate and water twice. The separated organic layer was concentrated under reduced pressure. The concentrated residue was chromatographed on column (chloroform/isopropanol=10/1, v/v). The purified solution was recovered and concentrated under reduced pressure. The residue was treated with ether for crystallization and with the addition of isopropyl ether (20 ml), and stirred for 2 hours, filtered and washed to give a desired compound of 1.77 g (yield: 73%).

Workup

  1. temperaturecooled
  2. stirringthe mixture was stirred at 5° C.˜10° C. for 3 hours
  3. temperatureThe solution was slowly heated
  4. stirringstirred at 15° C.˜20° C. for 30 minutes
  5. washThe solution was washed with an aqueous sodium bicarbonate and water twice
  6. concentrationThe separated organic layer was concentrated under reduced pressure
  7. customThe concentrated residue was chromatographed on column (chloroform/isopropanol=10/1
  8. customThe purified solution was recovered
  9. concentrationconcentrated under reduced pressure
  10. additionThe residue was treated with ether for crystallization and with the addition of isopropyl ether (20 ml)
  11. stirringstirred for 2 hours
  12. filtrationfiltered
  13. washwashed

Sources & evidence

ORD record
ord-b727f3d375fa45ab82b1ecbf9ccf89b5
Source dataset
uspto-grants-2001_10
Patent number
US06306860B1

Reaction notes

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