Cesium carbonate → HCID 71115228, compound

HRID 468793Notes

Reaction equation

HRID 468793 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21](B2OCC(C)(C)CO2)[CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.O.[Pd](Cl)Cl.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[C:25]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH:26]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 115143254-Chloro-2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzonitrileHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 71115228HCID 71115228, compoundYield 5.8%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (200 mg, 0.68 mmol), 4-chloro-2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzonitrile (205 mg, 0.816 mmol), cesium carbonate (0.22 g, 0.68 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine) palladium dichloride (24.0 mg, 0.05 eq) in a mixture of acetonitrile and water (10 mL, 10:1) was purged with nitrogen and stirred at 90° C. for 45 minutes under microwave irradiation. Ethyl acetate (20 mL) was added to the reaction mixture and it was filtered. The solid was extracted with ethyl acetate (20 mL×4). The combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by HPLC separation to give the product (13.7 mg, 5.8%). LCMS (ESI): RT (min)=1.099, M+H+=347.9, method=A. 1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.24 (s, 1H), 8.54 (s, 1H), 8.33 (t, J=0.8 Hz, 1H), 8.08-7.72 (m, 5H), 2.09-2.05 (m, 1H), 0.88-0.83 (m, 4H).

Workup

  1. customwas purged with nitrogen
  2. additionEthyl acetate (20 mL) was added to the reaction mixture and it
  3. filtrationwas filtered
  4. extractionThe solid was extracted with ethyl acetate (20 mL×4)
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by HPLC separation

Sources & evidence

ORD record
ord-ad49e4f06f9d4733aaeb79d323df8498
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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