Potassium Carbonate → 5-{[1-(2,5-dimethylphenyl)-3-(4-fluorophenyl)-1H-pyrazol-5-yl]amino}-2-(methylthio)pyrimidine-4-carboxylic acid

HRID 2109937Notes

Reaction equation

Cl[C:2]1[C:3]([C:10]([OH:12])=[O:11])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][C:21]=1[N:27]1[C:31]([NH2:32])=[CH:30][C:29]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)=[N:28]1>CN(C=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][C:21]=1[N:27]1[C:31]([NH:32][C:2]2[C:3]([C:10]([OH:12])=[O:11])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=2)=[CH:30][C:29]([C:33]2[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=2)=[N:28]1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 5-chloro-2-(methylthio)pyrimidine-4-carboxylic acid (89 mg, 0.44 mmol), potassium carbonate (66 mg, 0.48 mmol), 1-(2,5-dimethylphenyl)-3-(4-fluorophenyl)-1H-pyrazol-5-amine (123 mg, 0.44 mmol), synthesized in a similar manner as Intermediate G, and copper (II) acetate (1.6 mg, 0.009 mmol) in DMF (1 mL) was heated (150° C.) in a sealed tube for 16 h. The mixture was cooled to rt, filtered through a silica gel plug using ethyl acetate as eluent, concentrated to dryness, and subjected to HPLC purification using a gradient elution from 30% to 90% acetonitrile in water to afford 24.2 mg (12.3%) of the desired product. 1H NMR (300 MHz, CD2Cl2) δ 8.95 (s, 1H), 8.90 (s, 1H), 7.85 (dd, 2H), 7.10-7.28 (m, 5H), 7.62 (s, 1H), 2.58 (s, 3H), 2.38 (s, 3H), 2.14 (s, 3H); ES-MS m/z 406.3 (MH+-CO2), HPLC RT (min) 4.07.

Workup

temperatureThe mixture was cooled to rt
filtrationfiltered through a silica gel plug
concentrationconcentrated to dryness
customsubjected to HPLC purification
washa gradient elution from 30% to 90% acetonitrile in water

Sources & evidence

ORD record: ord-ba9b809122564a63af4808938963c20f
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07517878B2

Reaction notes

Loading…