Dimethyl Sulfate → HCID 67958038, compound

HRID 1529428Notes

Reaction equation

[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]([OH:22])=[O:21])[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2].[C:23]([O-])([O-])=O.[K+].[K+].S(OC)(OC)(=O)=O>CN(C=O)C>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]([O:22][CH3:23])=[O:21])[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-(6-isopropoxy-pyrazin-2-yl)-1H-indole-3-carboxylic acid (8.0 g, 26.9 mmol) in DMF (80 mL) was added K2CO3 (4.50 g, 32.3 mmol) and dimethyl sulfate (2.50 mL, 26.9 mmol) at RT and the reaction was heated to 80° C. for 3 h. The mixture was cooled to RT and partitioned between ice water (80 mL) and EtOAc (80 mL). The organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified with silica gel chromatography (eluting with 15% EtOAc in petroleum ether) to give methyl 5-(6-isopropoxypyrazin-2-yl)-1H-indole-3-carboxylate (6.5 g, 79%) as an off white solid. MS (ESI, pos. ion) m/z: 311.9 (M+1); 1H-NMR (DMSO-d6) δ ppm; 8.70 (d, J=1.6 Hz, 2H), 8.18 (s, 1H), 8.14 (s, 1H), 7.9 (dd, J=2.0 Hz, 1H), 7.62 (d, J=8.4, 1.6 Hz, 1H), 5.39-5.43 (m, 1H), 3.85 (s, 3H), 1.40 (d, J=6.0 Hz, 6H).

Workup

temperatureThe mixture was cooled to RT
custompartitioned between ice water (80 mL) and EtOAc (80 mL)
customThe organic layer was separated
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified with silica gel chromatography (eluting with 15% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-55c4fa47dcd141af9f50853a242745e4
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

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