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Hydrochloric Acid → 2-[(S)-4-(4-Benzyl-phthalazin-1-yl)-2-methoxycarbonyl-piperazin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester

HRID 42191
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HRID 42191 반응식
[CH3:1][O:2][C:3]([C@H:5]1[N:10]([C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[C:14]([C:21]([O:23][CH3:24])=[O:22])=[CH:13][N:12]=2)[CH2:9][CH2:8][N:7]([C:25](OC(C)(C)C)=O)[CH2:6]1)=[O:4].Cl.[CH2:33]([C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)C(Cl)=[N:42][N:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH2:51](N(CC)CC)C>C(OCC)C.C(Cl)Cl>[CH2:24]([O:23][C:21]([C:14]1[C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]([N:10]2[CH2:9][CH2:8][N:7]([C:25]3[C:48]4[C:49](=[CH:44][CH:45]=[CH:46][CH:47]=4)[C:40]([CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[N:41][N:42]=3)[CH2:6][C@H:5]2[C:3]([O:2][CH3:1])=[O:4])=[N:12][CH:13]=1)=[O:22])[CH3:51]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 64045661-Benzyl-4-chlorophthalazineHCID 68707290(S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-ester

생성물 1

HCID 592406482-[(S)-4-(4-Benzyl-phthalazin-1-yl)-2-methoxycarbonyl-piperazin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester
수율 8%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매

실험 절차

To a methylene chloride (0.02M) solution of (S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-ester (69 mg, 0.153 mmol), is added 1N HCl (2 mmol), 2M in diethyl ether. Stir reaction mixture at room temperature for 18 h. Concentrate and dilute with dioxane (0.1 M), followed by addition of 1-benzyl-4-chloro-phthalazine (0.153 mmol) and triethylamine (0.459 mmol). Microwave reaction mixture for 30 min at 150° C. MS shows some starting material still present. Microwave for an additional 2.5 h at 150° C. Concentrate reaction mixture and purify by column chromatography 0-75% ethyl acetate/heptane gradient to afford the title compound. (8% yield)

후처리

  1. customreaction mixture at room temperature for 18 h
  2. concentrationConcentrate
  3. additiondilute with dioxane (0.1 M)
  4. customMicrowave reaction mixture for 30 min at 150° C
  5. concentrationConcentrate
  6. customreaction mixture
  7. custompurify by column chromatography 0-75% ethyl acetate/heptane gradient

출처 및 근거

ORD 기록
ord-1fb9fdad713d49a7b704ceef49f7cac2
출처 데이터셋
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08536168B2

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