1,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene) → HCID 178490904, compound
Reaction equation
C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1.[CH3:26][O:27][C:28]1[CH:51]=[CH:50][C:31]([CH2:32][N:33]2[C:37]([NH:38][CH:39]=[C:40]3[C:45](=[O:46])OC(C)(C)OC3=O)=[CH:36][CH:35]=[N:34]2)=[CH:30][CH:29]=1>>[CH3:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([CH2:32][N:33]2[C:37]3[N:38]=[CH:39][CH:40]=[C:45]([OH:46])[C:36]=3[CH:35]=[N:34]2)=[CH:50][CH:51]=1Participants
Conditions
- Temperature
- 240 °C
Procedure
2,2-dimethyl-1,3-dioxane-4,6-dione 1 (meldrum's acid) (20 g, 139 mmol), 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (2) (28.2 g, 139 mmol, 1 eq) (prepared according to the procedure described by Misra, R. N., et al. Bioorg. Med. Chem. Lett. (2003), 13, 1133-1136) in presence of triethoxymethane (30.8 g, 208 mmol, 1 eq) was heated to 85° C. for 1 hr, subsequently worked up and treated with diethyl ether, and provided the pure 5-(((1-(4-methoxybenzyl)-1H-pyrazol-5-yl)amino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (3) as yellow solid (39.3 g). To a stirred solution of DOWTHERM™ (80 mL) was added compound 3 (39.3 g at 200° C. under N2 in portions over a 30 min). After completion of additions, the RM was heated at 240° C. for 1 hr. After completion of the reaction from TLC, the mixture was diluted with hexanes (300 mL) to separate the DOWTHERM™ from the crude RM. The resulting crude mixture on treatment with DCM and diethyl ether provided the off-white solid of 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (4) (24.56 g). Chlorination of compound 4 (24 g, 94 mmol) on treatment with phosphoryl trichloride (43 g, 282 mmol) in dichloroethane (10 mL) at 40° C. for 4 hr yielded 19 g of 4-chloro-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine 5.
Workup
- customAfter completion of the reaction from TLC
- customto separate the DOWTHERM™ from the crude RM
Sources & evidence
- ORD record
- ord-e278abc7ba774f6d865aa798eaba58fa
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09260426B2
Reaction notes
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