1-Methyl-4-(piperidin-4-yl)piperazine → HCID 68496027, compound

HRID 388499Notes

Reaction equation

HRID 388499 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH2:4][CH2:3]1.[CH2:14]([O:21][C:22]([C:24]1([C:27](=[O:53])[NH:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]3[CH:41]=[CH:40][N:39]=[C:38]([NH:42][C:43](OC4C=CC=CC=4)=[O:44])[CH:37]=3)=[CH:31][C:30]=2[F:52])[CH2:26][CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN1CCCC1=O>[CH2:14]([O:21][C:22]([C:24]1([C:27](=[O:53])[NH:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH:36]3[CH2:41][CH2:40][NH:39][CH:38]([NH:42][C:43]([N:11]4[CH2:12][CH2:13][CH:8]([N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)[CH2:9][CH2:10]4)=[O:44])[CH2:37]3)=[CH:31][C:30]=2[F:52])[CH2:25][CH2:26]1)=[O:23])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

4

Reactant 2

HCID 7957071-Methyl-4-(piperidin-4-yl)piperazineHCID 247886951-[2-Fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

Product 1

HCID 68496027HCID 68496027, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
40 °C

Procedure

1-Methyl-4-(piperidin-4-yl)piperazine (1.46 g) was added to a mixture of 1-[2-fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (3.60 g) and N-methyl-2-pyrrolidone (25 ml), followed by stirring with heating at 40° C. for 1 hour and 51 minutes. The reaction mixture was partitioned after the addition of ethyl acetate (180 mL) and water (90 mL). The resultant organic layer was washed with water (36 ml, twice) and a 10% aqueous solution of sodium chloride (36 ml), dried over anhydrous magnesium sulfate (10 g), and filtered, and the filtrate was concentrated. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:1, ethyl acetate, ethyl acetate:isopropyl alcohol=9:1). The eluate was concentrated under reduced pressure, and the precipitate appeared after the addition of tert-butyl methyl ether (60 ml) and seed crystals obtained in (Method 1). The resultant precipitate was collected by filtration, washed with tert-butyl methyl ether (10 ml), and dried under reduced pressure at 40° C. for 2 hours to give the target title compound (2.57 g).

Workup

  1. customThe reaction mixture was partitioned
  2. additionafter the addition of ethyl acetate (180 mL) and water (90 mL)
  3. washThe resultant organic layer was washed with water (36 ml
  4. dry with materialtwice) and a 10% aqueous solution of sodium chloride (36 ml), dried over anhydrous magnesium sulfate (10 g)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:1, ethyl acetate, ethyl acetate:isopropyl alcohol=9:1)
  8. concentrationThe eluate was concentrated under reduced pressure
  9. additionafter the addition of tert-butyl methyl ether (60 ml) and seed crystals
  10. customobtained in (Method 1)
  11. filtrationThe resultant precipitate was collected by filtration
  12. washwashed with tert-butyl methyl ether (10 ml)
  13. customdried under reduced pressure at 40° C. for 2 hours

Sources & evidence

ORD record
ord-a1fbd0597a354343a44111386b2f8347
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

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