Water → Imnopitant

HRID 379413

反応式

HRID 379413 の反応式
[CH3:1][NH:2][C:3](=[O:24])[C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[CH:8][C:7]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[N:6][CH:5]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:35][C:36]([F:50])([F:49])[C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:40]Br.O>C1COCC1>[F:35][C:36]([F:50])([F:49])[C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:40][N:2]([CH3:1])[C:3](=[O:24])[C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[CH:8][C:7]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[N:6][CH:5]=1

参加物

6

反応物 4

HCID 962WaterHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 15481065N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide

生成物 1

HCID 9808518Imnopitant収率 84.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2.5 g (7.7 mmol) N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide in 51 ml THF at 4° C. was added dropwise over 30 min 10.2 ml (10.2 mmol) potassium bis(trimethylsilyl) amide (1M in THF). The reaction mixture was stirred for 30 min and subsequently treated at 4° C. dropwise over 30 min with 1.46 ml (7.7 mmol) 3,5-bis-trifluoromethyl-benzylbromide. The reaction mixture was stirred for 1.5 h at 4° C., treated with 31 ml water and extracted. The aqueous phase was separated and adjusted to pH 12 with 2N NaOH and subsequently extracted with 30 ml ethyl acetate. The aqueous phase was separated, the combined organic phases were dried over Na2SO4, the solvent was removed under reduced pressure and the residue purified by chromatography over silica gel (CH2Cl2: MeOH=99:1) to yield 3.6 g (84.1%) product as beige foam.

後処理

  1. stirringThe reaction mixture was stirred for 1.5 h at 4° C.
  2. extractionextracted
  3. customThe aqueous phase was separated
  4. extractionsubsequently extracted with 30 ml ethyl acetate
  5. customThe aqueous phase was separated
  6. dry with materialthe combined organic phases were dried over Na2SO4
  7. customthe solvent was removed under reduced pressure
  8. customthe residue purified by chromatography over silica gel (CH2Cl2: MeOH=99:1)

出典と根拠

ORDレコード
ord-1ec4ad1853394c35b52f2cde54435ba3
出典データセット
uspto-grants-2001_10
特許番号
US06297375B1

関連ノート

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