Ethanol → (5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanol

HRID 589448Notes

Reaction equation

HRID 589448 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11](OC)=[O:12])=[N:9][N:8]([C:15]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:5]2=[N:6][CH:7]=1.CCO.[Li+].[BH4-]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][OH:12])=[N:9][N:8]([C:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 4148881Lithium borohydrideHCID 86701062methyl 5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carboxylate

Product 1

HCID 86701061(5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanolYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XXII) (4.16 Kg, 8.3 mol) in anhydrous THF (62 L) cooled to 10° C. was added anhydrous EtOH (0.97 L, 16.6 mol) and LiBH4 (271 g, 12.5 mol). The reaction was warmed to room temperature and stirred for 24 hours. The solution was concentrated under vacuum to a volume of 4 L then taken up in DCM (80 L). The pH was then adjusted to 8.0 by dropwise addition of aqueous 0.4N HCl (˜280 L). The organic layer was separated and washed with aqueous 25% NaCl (28 L) and then concentrated under vacuum to a volume of 4 L to produce (5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanol (XXIII) (3.9 Kg, 8.3 mol, 82.3% purity, 100% assay yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm 4.70 (d, J=6 Hz, 2H), 5.49 (t, J=6 Hz, 1H), 7.19 (d, J=7.2 Hz, 5H), 7.20-7.35 (m, 10H), 8.31 (d, J=2.4 Hz, 1H), 8.51 (d, J=2.4 Hz, 1H); ESIMS found C26H20BrN3O m/z 492.0 (M+Na).

Workup

  1. concentrationThe solution was concentrated under vacuum to a volume of 4 L
  2. additionThe pH was then adjusted to 8.0 by dropwise addition of aqueous 0.4N HCl (˜280 L)
  3. customThe organic layer was separated
  4. washwashed with aqueous 25% NaCl (28 L)
  5. concentrationconcentrated under vacuum to a volume of 4 L

Sources & evidence

ORD record
ord-10cb3512b5f74f7eb135f287d1b22fe0
Source dataset
uspto-grants-2016_01
Patent number
US09233104B2

Reaction notes

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