Hydrazine → HCID 25099584, 화합물

HRID 2381926노트

반응식

HRID 2381926 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([N:17]2C(=O)C3C(=CC=CC=3)[C:18]2=[O:27])[C:13](=[O:28])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NN.[C:31]1([C:37]2[N:42]=[CH:41][C:40](C(Cl)=O)=[CH:39][N:38]=2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CO.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([NH:17][C:18]([C:40]2[CH:41]=[N:42][C:37]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[N:38][CH:39]=2)=[O:27])[C:13](=[O:28])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 9321HydrazineHCID 106326372-phenylpyrimidine-5-carbonyl ChlorideHCID 68554807HCID 68554807, 화합물

생성물 1

HCID 25099584HCID 25099584, 화합물수율 183.8%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of 4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-oxo-piperazine-1-carboxylic acid benzyl ester (53 mg, 0.14 mmol) in MeOH (10 mL) is treated with anhydrous hydrazine (0.3 mL, 9.56 mmol). The reaction mixture is stirred at reflux under N2 for 3.5 h. The reaction mixture is concentrated. The residue is dissolved in a mixture of DMF (2 mL) and DCM (2 mL), and treated with 2-phenyl-pyrimidine-5-carbonyl chloride (32 mg, 0.15 mmol). The mixture is stirred under N2 for 16 h, and then diluted with EtOAc (35 mL). The mixture is washed successively with saturated aqueous KHCO3, (15 mL), water (2×15 mL), and saturated aqueous NaCl (15 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue is purified by flash silica gel chromatography (80:20 to 0:100 heptane:EtOAc gradient elution) to afford 3-oxo-4-[(2-phenyl-pyrimidine-5-carbonyl)-amino]-piperazine-1-carboxylic acid benzyl ester as an oil (111 mg, 18%). MS: 432 (M+H); 1H NMR (300 MHz, CDCl3) δ 9.70-10.10 (br, 1H), 9.06 (s, 2H), 8.46 (dd, J=7.8, 1.7 Hz, 2H), 7.44-7.60 (m, 3H), 7.25-7.40 (m, 5H), 5.18 (s, 2H), 4.36 (s, 2H), 3.93 (t, J=5.1 Hz, 2H), 3.69-3.81 (br s, 2H). IC50=103.5 nM.

후처리

  1. temperatureat reflux under N2 for 3.5 h
  2. concentrationThe reaction mixture is concentrated
  3. dissolutionThe residue is dissolved in a mixture of DMF (2 mL) and DCM (2 mL)
  4. stirringThe mixture is stirred under N2 for 16 h
  5. washThe mixture is washed successively with saturated aqueous KHCO3, (15 mL), water (2×15 mL), and saturated aqueous NaCl (15 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by flash silica gel chromatography (80:20 to 0:100 heptane:EtOAc gradient elution)

출처 및 근거

ORD 기록
ord-dfacef70dc1d44e2beb206eb349648b2
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08258130B2

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