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

HRID 584194노트

반응식

HRID 584194 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 62652Cuprous chloride촉매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-05cba58a22fd4a008e038b2fd3de8e97
출처 데이터셋
uspto-grants-2005_08
특허 번호
US06924278B2

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