Methylamine → HCID 15491311, compound

HRID 895343Notes

Reaction equation

HRID 895343 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:6][O:7][CH2:8][CH:9]([N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23](O)=[O:24])[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN.C1C=CC2N(O)N=[N:43][C:41]=2C=1.C(N(C(C)C)CC)(C)C.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1.C(#N)C>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=1)[CH2:6][O:7][CH2:8][CH:9]([N:16]1[CH2:17][CH2:18][N:19]([CH2:22][C:23]([NH:43][CH3:41])=[O:24])[CH2:20][CH2:21]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 5

HCID 6329MethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10141196HCID 10141196, compound2×

Product 1

HCID 15491311HCID 15491311, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a round-bottomed flask fitted with a reflux condenser and a thermometer are introduced 1.5 g (3 mmoles) of {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-acetic acid (compound 229 prepared at example 1.4.2 above), 7 ml of THF and 7 ml of acetonitrile. Then 1.85 ml (3.7 mmoles) of a 2M solution of methylamine in THF are added, followed by 234 mg (1.5 mmoles) of HOBT, 1.33 ml (7.6 mmoles) of diisopropylethylamine and 880 mg (4.3 mmoles) of DCC. The mixture is stirred until completion of the reaction, and filtered. Volatile substances are removed under reduced pressure, and the residue is partitioned between ethyl acetate and 0.1 N sodium hydroxide. The organic phase is washed with brine, dried over magnesium sulfate and volatile substances are removed under reduced pressure. This yields crude 2-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-N-methyl-acetamide (compound 292) which is directly converted into its dimaleate salt in 2-butanone (1.44 g of a white solid; yield 65%).

Workup

  1. customIn a round-bottomed flask fitted with a reflux condenser
  2. filtrationfiltered
  3. customVolatile substances are removed under reduced pressure
  4. customthe residue is partitioned between ethyl acetate and 0.1 N sodium hydroxide
  5. washThe organic phase is washed with brine
  6. dry with materialdried over magnesium sulfate and volatile substances
  7. customare removed under reduced pressure

Sources & evidence

ORD record
ord-9d6b916a3ca04667a048d36e30823ad9
Source dataset
uspto-grants-2005_07
Patent number
US06916797B2

Reaction notes

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