Hydrochloric Acid → ethanesulfonic acid (2-hydroxy-ethyl)-[5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide

HRID 1630951Notes

Reaction equation

HRID 1630951 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+].Cl[CH2:26][CH2:27][O:28][Si](C)(C)C.Cl>CN(C=O)C>[OH:28][CH2:27][CH2:26][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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 2628232-ChloroethoxytrimethylsilaneHCID 59534642ethanesulfonic acid [5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide

Product 1

HCID 58215743ethanesulfonic acid (2-hydroxy-ethyl)-[5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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, 200 mg, 0.634 mmol) and DMF (3 mL). The reaction is cooled to 0° C. and sodium hydride (38.0 mg, 0.951 mmol) is added. The reaction is stirred at room temperature for 10 min, then 2-chloro-ethoxytrimethylsilane (0.154 mL, 0.951 mmol) is added. The reaction is stirred at 100° C. for 16 h then cooled to room temperature. Aqueous 1M HCl (1 mL) is added and stirring is continued for 30 min. The mixture is purified using an Xbridge C18 eluting with a 10 to 100% acetonitrile-water gradient to afford ethanesulfonic acid (2-hydroxy-ethyl)-[5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide. MS (ESI) m/z 360.1 (M+H)+. 1H NMR (400 MHz, MeOD) δ ppm 1.42 (t, J=7.3 Hz, 3H), 3.29 (t, 2H), 3.70 (t, J=5.6 Hz, 2H), 3.84 (s, 3H), 3.96 (t, J=5.6 Hz, 2H), 6.75 (s, 1H), 7.14 (td, J=7.5, 0.9 Hz, 1H), 7.28 (td, J=7.7, 1.0 Hz, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 8.18 (t, J=2.1 Hz, 1H), 8.71 (d, J=2.3 Hz, 1H), 8.75 (d, J=1.8 Hz, 1H). HRMS (ESI) m/z 360.1383 [(M+H)+ Calcd for C18H12N3O3S 360.1376].

Workup

  1. stirringThe reaction is stirred at 100° C. for 16 h
  2. temperaturethen cooled to room temperature
  3. stirringstirring
  4. waitis continued for 30 min
  5. customThe mixture is purified
  6. washC18 eluting with a 10 to 100% acetonitrile-water gradient

Sources & evidence

ORD record
ord-d321197f5adb410eb5d570e6b20d0532
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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