Sodium Carbonate → 4-(5-Amino-6-methylisoquinolin-1-ylamino)benzonitrile

HRID 1042251Notes

Reaction equation

[CH3:1][C:2]1[C:3]([N+:21]([O-])=O)=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([NH:12][C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=1)=[N:7][CH:6]=[CH:5]2.O.O.[Sn](Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CCO>[NH2:21][C:3]1[C:2]([CH3:1])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][N:7]=[C:8]2[NH:12][C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 4-(6-methyl-5-nitroisoquinolin-1-ylamino)benzonitrile (0.47 g, 1.5 mmol), tin(II) chloride dihydrate (1.8 g, 7.7 mmol) and absolute EtOH (50 mL) was stirred under N2 at 70° C. for 17 h. The crude reaction mixture was poured onto ˜100 mL ice. The resulting solution was treated with solid Na2CO3 to pH 10. The milky yellow suspension was extracted with EtOAc (3×150 mL). The combined EtOAc extracts were washed with saturated NaCl (100 mL), dried over Na2SO4, filtered and concentrated in vacuo to give 510 mg as a red solid. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 1% to 5% MeOH in CH2Cl2, to provide 4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile (0.29 g, 68% yield) as a red solid. MS (ESI, pos. ion) m/z: 275 [M+H]+.

Workup

customThe crude reaction mixture
extractionThe milky yellow suspension was extracted with EtOAc (3×150 mL)
washThe combined EtOAc extracts were washed with saturated NaCl (100 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customto give 510 mg as a red solid
customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
washeluting with a gradient of 1% to 5% MeOH in CH2Cl2

Sources & evidence

ORD record: ord-d2618489b4b64652af55b85d8432d878
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08557830B2

Reaction notes

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