Methylamine → tert-butyl 4-((3-bromo-6-(methylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate

HRID 928229Notes

Reaction equation

[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7](SC)=[N:8][CH:9]=2)[N:4]([CH2:13][CH:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]2)[N:3]=1.ClC1C=C(C=CC=1)C(OO)=O.[CH3:39][NH2:40]>C(Cl)Cl.CCOC(C)=O.C1COCC1>[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([NH:40][CH3:39])=[N:8][CH:9]=2)[N:4]([CH2:13][CH:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]2)[N:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of tert-butyl 4-((3-bromo-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.91 g, 2.0 mmol) in CH2Cl2 (30 mL) was added meta-Chloroperoxybenzoic acid (1.34 g, 77%, 6 mmol) at room temperature. The color of the solution changed to light purple from colorless. After 2 h, the reaction was diluted with EtOAc. The organic solution was then washed with 1 N NaOH (3×), dried (NaSO4), and concentrated. The resulting residue was dissolved in THF (10 mL) before a 2.0 M methylamine solution in THF (10 mL, 20 mmol) was added at room temperature. The resulting solution was heated at 60° C. for 2 h. After removal of the solvent, it was purified by Isco to provide tert-butyl 4-((3-bromo-6-(methylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.75 g, 85%) as a white solid. MS m/z 439.2 [M+H]+.

Workup

washThe organic solution was then washed with 1 N NaOH (3×)
dry with materialdried (NaSO4)
concentrationconcentrated
additionwas added at room temperature
customAfter removal of the solvent, it
customwas purified by Isco

Sources & evidence

ORD record: ord-18fd897d1aea412687f95c06ae2c7739
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290499B2

Reaction notes

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