Water → 5-{7-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3,4-dihydroisoquinolin-2(1H)-yl}pyridine-2-carbonitrile

HRID 449329Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=[C:4]([NH2:15])[N:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:33]=[C:32]3[C:27]([CH2:28][CH2:29][N:30]([C:34]4[CH:35]=[CH:36][C:37]([C:40]#[N:41])=[N:38][CH:39]=4)[CH2:31]3)=[CH:26][CH:25]=2)O1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.CO>[NH2:15][C:4]1[N:3]=[C:2]([C:24]2[CH:33]=[C:32]3[C:27]([CH2:28][CH2:29][N:30]([C:34]4[CH:35]=[CH:36][C:37]([C:40]#[N:41])=[N:38][CH:39]=4)[CH2:31]3)=[CH:26][CH:25]=2)[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (0.075 g, 0.33 mmol), 5-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyridine-2-carbonitrile (0.12 g, 0.33 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane (1:1) complex (0.01 g, 0.02 mmol) and potassium carbonate (0.14 g, 0.99 mmol) in 1,4-dioxane (2 mL), and water (1 mL) was heated at 120° C. for 2 h. After cooled to r.t., the mixture was diluted with MeOH, filtered, concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with 10% MeOH in DCM to give the desired product. The product was further purified by RP-LCMS (pH=10) to afford the desired product (0.10 g, yield: 71%). Analytic LCMS (M+H)+: m/z=427.3.

Workup

temperatureAfter cooled to r.t.
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by flash chromatography on a silica gel column
washeluting with 10% MeOH in DCM

Sources & evidence

ORD record: ord-91c47c5487424d27bb2d7b01947d3433
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481732B2

Reaction notes

Loading…