Cesium carbonate → HCID 68158245, compound

HRID 243496Notes

Reaction equation

HRID 243496 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:17]([CH3:18])[C:16]3[C:19](Br)=[CH:20][CH:21]=[CH:22][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1.[C:24]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)#[N:25].C([O-])([O-])=O.[Cs+].[Cs+]>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][C@H:11]([C:13]2[N:17]([CH3:18])[C:16]3[C:19]([C:30]4[CH:29]=[CH:28][CH:27]=[C:26]([C:24]#[N:25])[CH:31]=4)=[CH:20][CH:21]=[CH:22][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27343253-Cyanophenylboronic acidHCID 68157965HCID 68157965, compound

Product 1

HCID 68158245HCID 68158245, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-amino-6-[(S)-1-(7-bromo-1-methyl-1H-benzoimidazol-2-yl)ethylamino]pyrimidine-5-carbonitrile (100 mg, 0.27 mmol), 3-cyanobenzeneboronic acid (51 mg, 0.35 mmol), Pd(PPh3)4 (31 mg, 0.03 mmol) and Cs2CO3 (175 mg, 0.54 mmol) in dioxane (3 mL) and H2O (1.5 mL) was heated for 30 min by microwave irradiation at 140° C. The reaction solution was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH, followed by 2M NH3 in MeOH. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PPC, gradient 0-10% 2M NH3 in MeOH/DCM) to afford 422 as a white solid (41 mg, 39%). LCMS (Method K): RT 3.08 min [M+H]+ 395. 1H NMR (DMSO-d6, 400 MHz): δ 8.03 (1H, s), 7.97 (1H, s), 7.94-7.91 (1H, m), 7.82-7.80 (1H, m), 7.72-7.66 (3H, m), 7.32 (2H, bs), 7.26 (1H, dd, J=8.0, 7.5 Hz), 7.07 (1H, dd, J=7.5, 1.0 Hz), 5.65 (1H, dq, J=7.0, 7.0 Hz), 3.29 (3H, s), 1.60 (3H, d, J=7.0 Hz)

Workup

  1. washThe cartridge was washed with MeOH
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (Si—PPC, gradient 0-10% 2M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-b13bcbbecb5c4db78eed6572975a64eb
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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