2,2-Dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl ester → 2,2-Dimethyl-propionic acid 5-bromo-3-(3-chloro-benzyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

HRID 1865639Notes

Reaction equation

HRID 1865639 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.[Cl-].[Cl:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25][Zn+]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH2:25][C:24]3[CH:27]=[CH:28][CH:29]=[C:22]([Cl:21])[CH:23]=3)=[N:9][N:8]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 579757462,2-Dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl esterHCID 178478087HCID 178478087, compound

Product 1

HCID 686623032,2-Dimethyl-propionic acid 5-bromo-3-(3-chloro-benzyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

2,2-Dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (1.46 g, 3.33 mmol), 3-chlorobenzylzinc chloride (0.5 M in tetrahydrofuran, 6.8 ml, 3.40 mmol), tetrakis(triphenylphoshino)palladium(0) (384 mg, 0.33 mmol), and tetrahydrofuran (10 ml) were combined and stirred for 18 hours at 50° C. The reaction was quenched with saturated, aqueous ammonium chloride, and extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography (0 to 10% ethyl acetate in hexanes) to give 436 mg (30%) of 2,2-dimethyl-propionic acid 5-bromo-3-(3-chloro-benzyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester. 1H-NMR (250 MHz, DMSO-d6) δ 8.56 (s, 1H), 7.88 (s, 1H), 7.24-7.18 (m, 4H), 6.41 (s, 2H), 4.25 (s, 2H), 1.18 (s, 9H); MS: m/z 436.1, 438.1 (M+H+).

Workup

  1. customThe reaction was quenched with saturated, aqueous ammonium chloride
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (0 to 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2cdde49c236f4befb3c029e154980a0f
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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