Trityl chloride → methyl 5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carboxylate

HRID 589447Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.Cl[C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[N:9][N:8]([C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XVII) (2.92 Kg, 11.4 mol) in anhydrous DCM (88 L) was added TEA (2.38 L, 17.1 mol). The solution was cooled to 0° C. before adding dropwise a solution of TrCl (4.0 Kg, 14.3 mol) in anhydrous DCM (51 L). The solution was warmed to room temperature and stirred for 20 hours. The reaction was then washed once with water (29 L), once with aqueous 25% NaCl (29 L), dried over Na2SO4 and concentrated to a volume of 3.0 L to give methyl 5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XXII) (5.69 Kg, 11.4 mol, 77.3% purity, 99.5% assay yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm 3.91 (s, 3H), 7.19 (d, J=8.4 Hz, 5H), 7.21-7.32 (m, 10H), 8.45 (d, J=2.4 Hz, 1H), 8.61 (d, J=2 Hz, 1H); ESIMS found C27H20BrN3O2 m/z 520.0 (M+Na).

Workup

temperatureThe solution was warmed to room temperature
washThe reaction was then washed once with water (29 L), once with aqueous 25% NaCl (29 L)
dry with materialdried over Na2SO4
concentrationconcentrated to a volume of 3.0 L

Sources & evidence

ORD record: ord-f86165dab9c74cb6bcc77032b558ce6c
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233104B2

Reaction notes

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