Cesium carbonate → HCID 68095273, compound

HRID 1502312Notes

Reaction equation

HRID 1502312 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:24]=[CH:23][C:22](B(O)O)=[C:21]([CH3:28])[CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([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)=[C:21]([CH3:28])[CH:20]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 5017600(4-Chloro-2-methylphenyl)boronic acidHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 68095273HCID 68095273, compoundYield 41.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (200 mg, 0.68 mmol), 4-chloro-2-methylphenylboronic acid (138.72 mg, 0.816 mmol), cesium carbonate (268 mg, 0.816 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (25 mg, 0.05 eq) in acetonitrile/water (10 mL, 10:1) was stirred at 130° C. under microwave irradiation for 30 min under nitrogen. The reaction mixture was diluted with ethyl acetate (20 mL) and filtered. The solid was washed with ethyl acetate (20 mL×4). The organic layer was combined, dried over sodium sulfate, filtered and concentrated. The crude product was purified by prep-HPLC to give the desired product (94.6 mg, 41.3%). LCMS (ESI): RT (Min)=1.328, M+H+=336.8, method=A. 1H NMR (400 MHz, DMSO-d6) δ0.95 (s, 1H), 9.16 (s, 1H), 8.49 (s, 1H), 7.99 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.68 (dd, J=1.6, 8.4 Hz, 1H), 7.48-7.34 (m, 3H), 2.28 (s, 3H), 2.07-2.05 (m, 1H), 0.86-0.82 (m, 4H).

Workup

  1. filtrationfiltered
  2. washThe solid was washed with ethyl acetate (20 mL×4)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-560075bf43e647c2898c6cfece034573
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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