Cesium carbonate → HCID 59471997, compound

HRID 78633Notes

Reaction equation

HRID 78633 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:20]2[CH:30]=[CH:29][C:23]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[CH:22][CH:21]=2)=[N:6][C:7]=1[C:8]1[O:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2Br)=[N:11][N:12]=1.[S:31]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.Cl[Pd]Cl>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:20]2[CH:30]=[CH:29][C:23]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[CH:22][CH:21]=2)=[N:6][C:7]=1[C:8]1[O:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:33]2[CH:34]=[CH:35][S:31][CH:32]=2)=[N:11][N:12]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 581760Thiophene-3-boronic acidHCID 59471841HCID 59471841, compound

Product 1

HCID 59471997HCID 59471997, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-[5-amino-6-[5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide (50 mg, 0.108 mmol), thiophen-3-ylboronic acid (13.8 mg, 0.108 mmol), cesium carbonate (107 μL of 2M aqueous solution) and dichloropalladium; triphenylphosphane (7.55 mg, 0.0108 mmol) in dioxane (2 mL) was heated at 110° C. in the microwave for 1 h. The reaction mixture was cooled to room temperature and filtered. The filtrated was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were combined and lypholised to give the product as a yellow solid (7.4 mg, 17% yield); 1H NMR (400 MHz, DMSO) d 2.97 (m, 6H), 7.09 (m, 1H), 7.53 (m, 2H), 7.60 (m, 2H), 7.64 (m, 2H), 7.71-7.76 (m, 3H), 8.01 (m, 2H), 8.07 (m, 1H) and 8.95 (s, 1H) ppm; MS (ES−) 469.22

Workup

  1. filtrationfiltered
  2. customThe filtrated was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]

Sources & evidence

ORD record
ord-310bca3d4b4d4682bd85198eb67d48db
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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