Cesium carbonate → 2-(7-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)ethanol

HRID 1522609Notes

Reaction equation

[F:1][C:2]1[C:3]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[C:17]4[C:18](=[CH:22][NH:23][N:24]=4)[N:19]=[CH:20][CH:21]=3)[CH:12]=[CH:11][N:10]=2)=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.Br[CH2:26][CH2:27][OH:28].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.C(#N)C.O>[F:1][C:2]1[C:3]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[C:17]4[C:18](=[CH:22][N:23]([CH2:26][CH2:27][OH:28])[N:24]=4)[N:19]=[CH:20][CH:21]=3)[CH:12]=[CH:11][N:10]=2)=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

N-(3′-Fluoro-6′-methyl-2,2′-bipyridin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine (21 mg, 0.066 mmol), 2-bromoethanol (8.19 mg, 0.066 mmol) and cesium carbonate (42.7 mg, 0.131 mmol) were combined in DMF (5 mL). The mixture was heated at 120° C. for 30 minutes, then cooled and purified by preparative HPLC using a Phenomenex Gemini Prep 5 μm C18, 75×30 mm column eluting with a gradient of 20-70% 10 mmol NH4HCO3 in 20/80 (v/v) water/acetonitrile in 10 mmol NH4HCO3 in water to afford 2-(7-(3′-fluoro-6′-methyl-2,2′-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)ethanol (2.1 mg, 8.79% yield). 2-(7-(3′-Fluoro-6′-methyl-2,2′-bipyridin-4-ylamino)-1H-pyrazolo[4,3-b]pyridin-1-yl)ethanol containing fractions were concentrated and subsequently purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 5-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to afford the title compound as TFA salts.

Workup

temperaturecooled
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-59120f6019f845dda200f25ea81c4afb
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073918B2

Reaction notes

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