Formaldehyde → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S)-3-isopropylmorpholino)-2-butynyl]-2-(3,4-dimethylbenzyl)piperazine dihydrochloride

HRID 584194ノート

反応式

HRID 584194 の反応式
[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)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[CH:16])[CH2:10][C@H:9]1[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([CH3:25])[CH:19]=1)=[O:7].[ClH:35].[CH:36]([C@H:39]1[CH2:44][O:43][CH2:42][CH2:41][NH:40]1)([CH3:38])[CH3:37].[CH:45](NC(C)C)(C)C.C=O>O1CCOCC1.[Cu]Cl>[ClH:35].[ClH:35].[F:34][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[C:16][CH2:45][N:40]2[CH2:41][CH2:42][O:43][CH2:44][C@@H:39]2[CH:36]([CH3:38])[CH3:37])[CH2:10][C@H:9]1[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([CH3:25])[CH:19]=1)=[O:7]

参加物

7

反応物 4

HCID 712FormaldehydeHCID 7912DiisopropylamineHCID 53973560(2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-propargylpiperazineHCID 69677740(3S)-3-(propan-2-yl)morpholine hydrochloride

生成物 1

HCID 86596431(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S)-3-isopropylmorpholino)-2-butynyl]-2-(3,4-dimethylbenzyl)piperazine dihydrochloride収率 76.6%

試薬・触媒・溶媒 2

HCID 62652Cuprous chloride触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of (2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-propargylpiperazine (286 mg), (3S)-3-isopropylmorpholine hydrochloride (118 mg) and N,N-diisopropylamine (92 mg) in dioxane (3 ml) was stirred at room temperature. Paraformaldehyde (22 mg) and copper(I) chloride (10 mg) were added and the whole was stirred for 30 minutes and then heated at 80° C. for 4 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel using a mixture of hexane and ethyl acetate (1:1) as eluent. The obtained product was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S)-3-isopropylmorpholino)-2-butynyl]-2-(3,4-dimethylbenzyl)piperazine dihydrochloride (190 mg).

後処理

  1. stirringthe whole was stirred for 30 minutes
  2. temperatureheated at 80° C. for 4 hours
  3. filtrationThe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by column chromatography on silica gel using
  6. additiona mixture of hexane and ethyl acetate (1:1) as eluent
  7. dissolutionThe obtained product was dissolved in ethyl acetate
  8. additiontreated with 4N hydrogen chloride in ethyl acetate

出典と根拠

ORDレコード
ord-05cba58a22fd4a008e038b2fd3de8e97
出典データセット
uspto-grants-2005_08
特許番号
US06924278B2

反応ノート

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