Sodium Carbonate → 4-Amino-6-({1-[5-chloro-3-(5-cyanopyridin-3-yl)-4-fluoro-2-methoxyphenyl]ethyl}amino)pyrimidine-5-carbonitrile

HRID 2274118Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH:11]([C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([F:20])=[C:15](Br)[C:14]=2[O:22][CH3:23])[CH3:12])[N:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][CH:35]=[C:36]([CH:39]=2)[C:37]#[N:38])O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH:11]([C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([F:20])=[C:15]([C:32]3[CH:33]=[N:34][CH:35]=[C:36]([C:37]#[N:38])[CH:39]=3)[C:14]=2[O:22][CH3:23])[CH3:12])[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Into a microwave vial was added 4-amino-6-{[1-(3-bromo-5-chloro-4-fluoro-2-methoxyphenyl)ethyl]amino}pyrimidine-5-carbonitrile (8.0 mg, 0.020 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile (5.51 mg, 0.0240 mmol), a solution of sodium carbonate (48 μL, 0.050 mmol) in water (48 μL), 1,4-dioxane (0.2 mL, 2 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.4 mg, 0.0012 mmol). The mixture was bubbled with N2 for 5 minutes and heated at 90° C. for 2 h. Purification by preparative LCMS (pH 10) gave the desired compound (37% yield). LCMS calculated for C20H16ClFN7O (M+H)+: m/z=424.1. found: 424.1.

Workup

customThe mixture was bubbled with N2 for 5 minutes
customPurification by preparative LCMS (pH 10)

Sources & evidence

ORD record: ord-cd8ffdb0bb6f42d191ebb70898374263
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126948B2

Reaction notes

Loading…