Methyl iodide → HCID 86619307, compound

HRID 1157355Notes

Reaction equation

HRID 1157355 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[NH:20][C:21]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([Cl:29])[CH:24]=2)=[O:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:33]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N:20]([C:21]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([Cl:29])[CH:24]=2)=[O:22])[CH3:33])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86619308HCID 86619308, compound

Product 1

HCID 86619307HCID 86619307, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-{2-[(2-chloro-pyridine-4-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester (100 mg, prepared as described in Example 1, Steps A-C) was added to a suspension of sodium hydride (50% in oil, 24 mg) in tetrahydrofuran at 0° C. and the resulting mixture was stirred at 0° C. for 1 hour at which time iodomethane (0.03 ml) was added. The reaction mixture was stirred at room temperature for 3 hours, diluted with ethyl acetate, washed three times with water, dried over sodium sulfate and concentrated in vacuo. The residue was subjected to silica gel chromatography (cyclohexane:ethyl acetate 7:3) to afford 4-{2-[(2-Chloro-pyridine-4-carbonyl)-methyl-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester as white crystals. M.p. 59-61° C.; 1H NMR (400 MHz, CDCl3) 1.5 (s, 9H), 2.2 (m, 2H), 2.8 (m, 2H), 3.4 (m, 2H), 3.4 (s, 3H), 3.5 (m, 2H), 6.7 (m, 1H), 6.9 (m, 1H), 7.0-7.3 (m, 4H), 8.1 (m, 1H); MS (ES+) 331 (M+H+—CO2-isobutene), 375 (M+H+-isobutene), 431 (M+H+). This compound was treated according to Example 1 Step D to afford the title product as yellow crystals. M.p. 117-120° C.; 1H NMR (400 MHz, CDCl3) 2.4 (m, 2H), 2.5 (m, 2H), 2.6 (m, 2H), 2.9 (m, 2H), 3.2 (m, 2H), 3.5 (s, 3H), 3.5 (m, 2H), 6.2 (dt, J=18, 9 Hz, 1H), 6.5 (d, J=18 Hz, 1H), 6.8 (d, J=9 Hz, 1H), 6.9 (d, J=5 Hz, 1H), 7.0-7.3 (m, 6H), 8.1 (d, J=5 Hz, 1H); retention Time HPLC 2.17 min; MS (ES+) 481/483 (M+H+).

Workup

  1. additionwas added
  2. washwashed three times with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3ee821a0e95149aa8bace772a4d873f3
Source dataset
uspto-grants-2010_10
Patent number
US07807679B2

Reaction notes

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