Hydrazine → HCID 25099584, compound

HRID 2381926Notes

Reaction equation

HRID 2381926 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

HCID 25099584HCID 25099584, compoundYield 183.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-dfacef70dc1d44e2beb206eb349648b2
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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