Methylamine → HCID 57635858, compound

HRID 2109952Notes

Reaction equation

HRID 2109952 reaction equation
[CH3:1][C:2]([C:6]1[CH:10]=[C:9]([NH:11][C:12]2[N:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14](O)=[O:15])[N:8]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=2[O:28][CH3:29])[N:7]=1)([CH3:5])[CH2:3][CH3:4].C(Cl)(=O)C(Cl)=O.[CH3:36]N.C[C:39]#[N:40]>CN(C)C=O.O>[CH3:5][C:2]([C:6]1[CH:10]=[C:9]([NH:11][C:12]2[N:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([N:40]([CH3:39])[CH3:36])=[O:15])[N:8]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=2[O:28][CH3:29])[N:7]=1)([CH3:1])[CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 6342AcetonitrileHCID 65578Oxalyl chlorideHCID 44193603HCID 44193603, compound

Product 1

HCID 57635858HCID 57635858, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 962WaterSolvent

Procedure

To a solution 2-{[3-(1,1-dimethylpropyl)-1-(3-fluoro-2-methoxyphenyl)-1H-pyrazol-5-yl]amino}nicotinic acid, (Example 140, synthesized in a manner similar to that of Example 8, 50 mg, 0.13 mmol) in CH3CN (1 mL) was added 1 drop of dimethyl formamide followed by oxalyl chloride (9 μL, 0.13 mmol). The mixture was stirred at rt for 1 h, followed by addition of methyl amine (16 μL of a 40% solution in water, 0.25 mmol). The mixture was again stirred at rt for 1 h and concentrated to dryness. The residue was dissolved in methanol (1 mL), filtered through an octyl solid phase extraction tube and subjected to HPLC purification with a gradient elution from 10% to 90% acetonitrile in water to afford 33 mg (70%) of the desired product. 1H NMR (300 MHz, CD2Cl2) δ 8.30 (d, 1H), 8.23 (s, 1H), 7.50 (d, 1H), 7.15-7.30 (m, 3H), 6.80 (t, 1H), 6.60 (s, 1H), 3.77 (s, 3H), 2.95 (br s, 6H), 1.70 (q, 2H), 1.32 (s, 6H), 0.85 (t, 3H). ES-MS m/z 426.2 (MH+); HPLC RT (min) 3.57.

Workup

  1. stirringThe mixture was again stirred at rt for 1 h
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in methanol (1 mL)
  4. filtrationfiltered through an octyl solid phase extraction tube
  5. customsubjected to HPLC purification with a gradient elution from 10% to 90% acetonitrile in water

Sources & evidence

ORD record
ord-8b70cc8c7fe2438fadcbbe0f22a6e7b1
Source dataset
uspto-grants-2009_04
Patent number
US07517878B2

Reaction notes

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