Methyl iodide → 2-(4-methoxyphenyl)-N-[6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-3-yl]acetamide

HRID 1672438Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[N:14]=[CH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([C:23]2[CH:24]=[N:25][NH:26][CH:27]=2)=[CH:18][CH:17]=3)=[O:11])=[CH:5][CH:4]=1.[C:28]([O-])([O-])=O.[Cs+].[Cs+].CI>O1CCOCC1.CS(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[N:14]=[CH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([C:23]2[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=2)=[CH:18][CH:17]=3)=[O:11])=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To the solution of 2-(4-Methoxy-phenyl)-N-[6-(1H-pyrazol-4-yl)-isoquinolin-3-yl]-acetamide (30.00 mg, 0.08 mmol) in 2 mL of dioxane was added Cs2CO3 (59.80 mg, 0.18 mmol) and CH3I (13.10 mg, 0.09 mmol). The mixture was heated at 70° C. for 72 hrs. Evaporation of the solvent gave the crude product which was re-dissolved in DMSO and purified by HPLC to give the title compound as a crystalline solid product (7.5 mg, 24.0%). 1H NMR (DMSO-d6, 400 MHz): δ 3.68 (2H, s), 3.73 (3H, s), 3.89 (3H, s), 6.89 (2H, d, J=8.5 Hz), 7.30 (2H, d, J=8.5 Hz), 7.75 (1H, dd, J=8.5, 1.5 Hz), 7.97-8.06 (2H, m), 8.08 (1H, s), 8.37 (2H, d, J=16.6 Hz), 9.03 (1H, s), 10.70 (1H, s). 13CNMR (DMSO-d6, 100 MHz): δ 42.19, 55.03, 106.31, 113.77, 120.33, 121.25, 123.88, 124.41, 127.88, 128.18, 128.9, 130.16, 134.93, 136.86, 137.86, 147.56, 150.80, 158.06, 170.78. HRMS: m/z 373.1660, calc. 373.1659. MS m/z, (APCI); 373.1 [(M+1)+100].

Workup

customEvaporation of the solvent
customgave the crude product which
custompurified by HPLC

Sources & evidence

ORD record: ord-ae95f397e74c4c17ba9816889ce99561
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07998978B2

Reaction notes

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