Sodium Iodide → HCID 178418757, compound

HRID 11830

Reaction equation

HRID 11830 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([C:7]2[N:8]=[C:9](Cl)[CH:10]=[C:11]([Cl:13])[N:12]=2)=[CH:5][CH:6]=1.[NH2:15][C:16]1[CH:20]=[C:19]([CH3:21])[NH:18][N:17]=1.C(N(CC)C(C)C)(C)C.[I-].[Na+]>C(O)CCC>[Cl:13][C:11]1[N:12]=[C:7]([C:4]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)[N:8]=[C:9]([NH:15][C:16]2[NH:17][N:18]=[C:19]([CH3:21])[CH:20]=2)[CH:10]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 77338FenclorimHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-

Product 1

HCID 178418757HCID 178418757, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
117 °C

Procedure

A suspension of Fenclorim (4,6-dichloro-2-phenylpyrimidine)(0.1 g, 0.44 mmol), 3-amino-5-methylpyrazole (0.045 g, 0.47 mmol), N,N-diisopropylethylamine (0.08 ml, 0.47 mmol) and sodium iodide (0.067 g, 0.44 mmol) in n-butanol (5 ml) were heated at 117° C. for 18 hours. The solvent was removed in vacuo and the crude product purified by flash chromatography (silica gel, 3:2 Petrol:EtOAc) to afford 0.037 g (29% yield) of (6-Chloro-2-phenyl-pyrimidin-4-yl)-(5-methyl-2H-pyrazol-3-yl)-amine as a off-white solid. A suspension of the above pyrimidine (0.037 g, 0.13 mmol) and thioacetamidothiophenol (0.108 g, 0.64 mmol) in tert-butanol was heated at 85° C. under nitrogen for 2 days. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. The concentrate was dissolved in EtOAc, and washed with NaHCO3 (sat, aq.). The organic layer is concentrated in vacuo, and the crude product by preperative HPLC. The residual disulfide that still remained in the mixture after HPLC may be removed by precipitation from EtOAc and filtration. The mother liquor was concentrated to afford IV-3 (7 mg, 13% yield) as an off-white solid: mp 235–236° C.; 1H NMR (DMSO) δ 2.10 (3H, s), 2.21 (3H, s), 6.33 (1H, br s), 7.50 (3H, m), 7.7–7.59 (2H, m), 7.76–7.78 (2H, m), 8.25 (2H, m), 9.72, 10.26 and 11.93 (3H, 3×br s); IR (solid) 1669, 1585, 1551, 1492, 1392, 1372, 1312, 1289, 1259, 1174, 1102, 1089, 1027, 1015, 984; MS 417.3 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe crude product purified by flash chromatography (silica gel, 3:2 Petrol:EtOAc)

Sources & evidence

ORD record
ord-112cf652bf9f4a6688b28ac649f63860
Source dataset
uspto-grants-2006_08
Patent number
US07098330B2

Linked notes

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