Phosphorus oxychloride → 6-Chloro-1-(1,1-dimethylethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid
Reaction equation
[CH3:1][C:2]([N:5]1[C:9]2[NH:10][C:11](=O)[CH:12]=[C:13]([C:14]([OH:16])=[O:15])[C:8]=2[C:7]([CH3:18])=[N:6]1)([CH3:4])[CH3:3].P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:11]1[CH:12]=[C:13]([C:14]([OH:16])=[O:15])[C:8]2[C:7]([CH3:18])=[N:6][N:5]([C:2]([CH3:4])([CH3:3])[CH3:1])[C:9]=2[N:10]=1Participants
Procedure
1-(1,1-Dimethylethyl)-3-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (5.07 g, 20.34 mmol) and phosphorus oxychloride (28.4 ml, 305 mmol) were heated at 100° C. for 16 hours. The contents were concentrated in vacuo. The residue was added to ice water followed by 1N NaOH until basic (pH>10). After stirring for 15 minutes, the mixture was adjusted to pH 3-4 by addition of 1N HCl. The contents were extracted with EtOAc, then washed with water, brine and concentrated in vacuo. The crude product was purified by reverse phase HPLC (40-70% ACN/H2O, 0.1% TFA). The product was collected as a solid, 0.50 g (9%). LCMS E-S (M+H)=268.3 1H NMR (400 MHz, DMSO-d6) δ ppm 1.73 (s, 9 H), 2.56 (s, 3 H), 7.48 (s, 1 H), 14.17 (br. s., 1 H).
Workup
- concentrationThe contents were concentrated in vacuo
- additionThe residue was added to ice water
- additionthe mixture was adjusted to pH 3-4 by addition of 1N HCl
- extractionThe contents were extracted with EtOAc
- washwashed with water, brine
- concentrationconcentrated in vacuo
- customThe crude product was purified by reverse phase HPLC (40-70% ACN/H2O, 0.1% TFA)
- customThe product was collected as a solid, 0.50 g (9%)
Sources & evidence
- ORD record
- ord-8b9baa8867e64fe19914b146e9c61f17
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073924B2
Reaction notes
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