Sodium Methoxide → HCID 44204556, compound

HRID 40680Notes

Reaction equation

[CH3:1][O-:2].[Na+].Br[C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[CH:13]=[N:12][C:11]([NH:15][C:16]1[N:17]=[CH:18][C:19]([C:22]#[N:23])=[N:20][CH:21]=1)=[CH:10]2>CN(C=O)C.[Cu](I)I>[CH3:1][O:2][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[CH:13]=[N:12][C:11]([NH:15][C:16]1[N:17]=[CH:18][C:19]([C:22]#[N:23])=[N:20][CH:21]=1)=[CH:10]2

Participants

Conditions

Temperature: 110 °C

Procedure

Sodium methoxide (55 mg, 0.10 mmol) was added to a pre-stirred mixture of 5-(8-bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile (33 mg, 0.10 mmol) and copper iodide (19 mg, 0.10 mmol) in DMF in triplicate. The three reaction mixtures were heated at 140° C. for 30 minutes, 110° C. for 18 hours, and 120° C. for 10 minutes, respectively. The combined reaction mixtures were partitioned between ethyl acetate and water and the aqueous layer re-extracted with more ethyl acetate. The combined organic phases were washed with brine, dried (Na2SO4), and concentrated in vacuo. Purification by preparative HPLC gave the title compound (1.7 mg, 0.006 mmol, 2%). 1H NMR (DMSO, 400 MHz) δ 9.33 (s, 1H), 8.81 (d, 1H, J=1.3 Hz), 8.71 (d, 1H, J=1.3 Hz), 8.43 (s, 1H), 7.64 (t, 1H, J=8.1 Hz), 7.43 (d, 1H, J=8.3 Hz), 6.97 (d, 1H, J=7.6 Hz), 4.01 (s, 3H). LCMS (2) Rt=2.87 min, m/z (ESI+) 278 (MH+).

Workup

customThe three reaction mixtures
customThe combined reaction mixtures
customwere partitioned between ethyl acetate and water
extractionthe aqueous layer re-extracted with more ethyl acetate
washThe combined organic phases were washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customPurification by preparative HPLC

Sources & evidence

ORD record: ord-9365a35055d6431690b2e8b053db835f
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530468B2

Reaction notes

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