1,4-Dioxane → HCID 57410847, compound

HRID 1502270Notes

Reaction equation

HRID 1502270 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.O1CCOCC1.C([Sn](CCCC)(CCCC)[C:29]1[CH:34]=[N:33][CH:32]=[CH:31][N:30]=1)CCC>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.C(OCC)(=O)C>[N:30]1[CH:31]=[CH:32][N:33]=[CH:34][C:29]=1[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

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 27373162-(Tributylstannyl)pyrazineHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 57410847HCID 57410847, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide 1 (42.8 mg, 0.147 mmol) and 1,4-Dioxane (1.5 mL, 19 mmol) was added 2-(tributylstannyl)pyrazine (51.0 uL, 0.162 mmol) and tetrakis(triphenylphosphine)palladium(0) (14.0 mg, 0.0121 mmol). The reaction mixture was subjected to microwave irradiation at 130° C. for 30 minutes. The reaction mixture is poured into ethyl acetate and washed with dilute NH4OH. The organic layer was dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 23.4 mg (55%) of N-(7-(pyrazin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=4.106, M+H=291.0, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 9.42 (s, 1H), 9.27 (s, 1H), 8.87 (s, 1H), 8.78 (s, 1H), 8.66 (s, 1H), 8.51 (s, 1H), 8.45 (d, J=8.6 Hz, 1H), 8.01 (d, J=8.7 Hz, 1H), 2.10 (s, 1H), 0.94-0.74 (m, 4H).

Workup

  1. customirradiation at 130° C. for 30 minutes
  2. washwashed with dilute NH4OH
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-72571f9f58f647a4a785ad2ac2970bca
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

Loading…