2-Hydrazinopyridine → 1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid N'-pyridine-2-yl-hydrazide

HRID 7903

Reaction equation

HRID 7903 reaction equation
[O:1]=[C:2]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[C:15]([OH:17])=O)[C:3](=[O:9])[C:4]([CH3:8])([CH3:7])[CH2:5][CH3:6].COC(=O)[C@@H]1CCCN1.[NH:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)[NH2:28].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C1COCC1.C(OCC)(=O)C.O>[N:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[NH:27][NH:28][C:15]([CH:11]1[CH2:12][CH2:13][CH2:14][N:10]1[C:2](=[O:1])[C:3](=[O:9])[C:4]([CH3:7])([CH3:8])[CH2:5][CH3:6])=[O:17]

Participants

10

Reactant 5

HCID 786452-HydrazinopyridineHCID 81531DiisopropylethylamineHCID 853477Methyl L-prolinateHCID 2733179PyBroPHCID 9837656Gpi-1485

Product 1

HCID 102684911-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid N'-pyridine-2-yl-hydrazide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidine-carboxylic acid (482 mg, 2 mmol), prepared from L-proline methyl ester according to the procedure described in WO 96/40633, 2-hydrazinopyridine (364 mg, 2 mmol), PyBrop (932 mg, 2 mmol), DMAP (4-dimethyaminopyridine, 122 mg) and DIEA (4 mL) in THF (dry, 50 mL) was stirred at room temperature for 24 h. Water and ethyl acetate were added. The organic phase was washed with ammonium chloride solution, followed by brine, and dried with MgSO4. Column chromatography (silica gel, ethyl acetate:methanol=10:0.5) gave a colorless oil; 490 mg (74%); MS (m/z) 333 (M+1); 1H NMR (d6-DMSO) δ0.85 (t, J=8 Hz, 3 H), 1.21 (s, 3 H), 1.23 (s, 3 H), 1.7 (m, 2 H), 1.90 (m, 1 H), 2.10 (m, 2 H), 2.35 (m, 1 H), 3.49 (t, J=8 Hz, 2 H), 4.62 (m, 1 H), 6.76 (m, 2 H), 7.51 (t, J=6 Hz, 1 H), 8.14 (d, J=6 Hz, 1 H).

Workup

  1. washThe organic phase was washed with ammonium chloride solution
  2. dry with materialdried with MgSO4
  3. customColumn chromatography (silica gel, ethyl acetate:methanol=10:0.5) gave a colorless oil

Sources & evidence

ORD record
ord-bd4a17db7fd44b94ad9c395a089d4e4a
Source dataset
uspto-grants-2006_08
Patent number
US07087628B2

Linked notes

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