Dimethyl Sulfate → HCID 25262918, compound

HRID 717233Notes

Reaction equation

[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:21])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])[N:7]([CH2:22][C@@H:23]2[CH2:27][CH2:26][CH2:25][O:24]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:28][O:29]S(OC)(=O)=O>C1(C)C=CC=CC=1>[C:23]([O-:29])(=[O:24])[CH3:27].[NH4+:6].[C:1]([C:5]1[N:6]([CH3:28])[N:7]([CH2:22][C@@H:23]2[CH2:27][CH2:26][CH2:25][O:24]2)[C:8](=[N:10][C:11](=[O:21])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 110 °C

Procedure

To the product from Example 12D (298 mg, 0.76 mmol) in toluene (6 mL) was added dimethylsulfate (0.145 mL, 1.52 mmol). The mixture was heated at 110° C. for 48 hours and concentrated under reduced pressure. The residue was dissolved in 1:1 dimethylsulfoxide/methanol and purified by reverse phase preparative HPLC on a Waters Nova-Pak® HR C18 6 um 60 Å Prep-Pak® cartridge column (40 mm×100 mm) using a gradient of 0% to 70% acetonitrile: 10 mM ammonium acetate over 8 min (10 min run time) at a flow rate of 70 mL/min to yield the title compound (150 mg, 48.6%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.36 (d, J=2.74 Hz, 1H), 7.27 (dd, J=8.77, 2.82 Hz, 1H), 6.98 (d, J=8.69 Hz, 1H), 6.80 (s, 1H), 4.26-4.37 (m, 2H), 4.12-4.20 (m, 1H), 3.87 (s, 3H), 3.73-3.78 (m, 1H), 3.72 (s, 3H), 3.59-3.66 (m, 1H), 1.67-1.92 (m, 4H), 1.37 (m, 9H). MS (ESI) m/z 406 (M+H)+.

Workup

concentrationconcentrated under reduced pressure
dissolutionThe residue was dissolved in 1:1 dimethylsulfoxide/methanol
custompurified by reverse phase preparative HPLC on a Waters Nova-Pak® HR

Sources & evidence

ORD record: ord-0d990358e44542469f54c5cc1606df51
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193713B2

Reaction notes

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