Methyl iodide → ethanesulfonic acid methyl-[5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide

HRID 1661727Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]1[CH:12]=[C:13]([NH:17][S:18]([CH2:21][CH3:22])(=[O:20])=[O:19])[CH:14]=[N:15][CH:16]=1.[H-].[Na+].[CH3:25]I>CN(C=O)C>[CH3:25][N:17]([C:13]1[CH:14]=[N:15][CH:16]=[C:11]([C:3]2[N:2]([CH3:1])[C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:12]=1)[S:18]([CH2:21][CH3:22])(=[O:20])=[O:19]

Participants

Conditions

Temperature: 0 °C

Procedure

A flask is charged with ethanesulfonic acid [5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide (Example 226, 100 mg, 0.317 mmol) and DMF (4 mL). The reaction is cooled to 0° C. and sodium hydride (15.85 mg, 0.396 mmol) is added. The reaction is stirred at 0° C. for 10 min, then methyl iodide (56.3 mg, 0.396 mmol) is added. The reaction is stirred for 1 hour at room temperature. The reaction is quenched with water (0.5 mL) and filtered. The filtrate is purified using Xbridge C18 eluting with a 10 to 100% acetonitrile-water gradient to afford ethanesulfonic acid methyl-[5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide. 1H NMR (400 MHz, MeOD) δ ppm 1.39 (t, J=7.5 Hz, 3H), 3.28 (q, J=7.5 Hz, 2H), 3.49 (s, 3H), 3.84 (s, 3H), 6.74 (s, 1H), 7.14 (t, J=7.6 Hz, 1H), 7.28 (ddd, J=7.6, 1.1 Hz, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.63 (d, J=7.8 Hz, 1H), 8.13 (t, J=2.1 Hz, 1H), 8.70 (d, J=2.0 Hz, 1H), 8.70 (d, J=2.5 Hz, 1H). HRMS (ESI) m/z 330.1281 [(M+H)+ Calcd for C17H19N3O2S 330.1270].

Workup

stirringThe reaction is stirred for 1 hour at room temperature
customThe reaction is quenched with water (0.5 mL)
filtrationfiltered
customThe filtrate is purified
washC18 eluting with a 10 to 100% acetonitrile-water gradient

Sources & evidence

ORD record: ord-a41ddc0fd0fe4950811d9598b3072dcb
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030334B2

Reaction notes

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