Cesium carbonate → HCID 67974827, compound

HRID 1502313Notes

Reaction equation

HRID 1502313 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:20]=[CH:21][C:22]([O:28][CH3:29])=[C:23](B(O)O)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.O.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]([O:28][CH3:29])=[C:21]([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:20]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27357515-Chloro-2-methoxyphenylboronic acidHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67974827HCID 67974827, compoundYield 10.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (150 mg, 0.595 mmol), 5-chloro-2-methoxyphenylboronic acid (132 mg, 0.714 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (24 mg, 0.03 mmol) and cesium carbonate (232 mg, 0.714 mmol) were mixed in acetonitrile and water (10:1, 20 mL). The reaction mixture was stirred at 120° C. under nitrogen for 6 hours. The reaction mixture was concentrated, diluted with water and extracted with ethyl acetate, concentrated and purified by prep-HPLC to give the desired product (21.3 mg, 10.2%). LCMS (ESI): RT (min)=1.216, M+H+=352.9, Method=I; 1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 9.14 (s, 1H), 8.46 (s, 1H), 8.12 (s, 1H), 7.84-7.42 (m, 4H), 7.18 (d, J=8.4 Hz, 1H), 3.78 (s, 3H), 2.09-2.05 (m, 1H), 0.88-0.83 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. concentrationconcentrated
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-431467ae5a514c5baa77164ad063dc0b
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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