Ethyl isocyanate → Ammonium Hydroxide

HRID 1630917Notes

Reaction equation

HRID 1630917 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[N:10]([CH3:21])[C:11]3[C:16]([C:17]=2[C:18]#[N:19])=[CH:15][CH:14]=[C:13]([Cl:20])[CH:12]=3)[CH:6]=[N:7][CH:8]=1.[CH2:22]([N:24]=[C:25]=[O:26])[CH3:23]>ClCCl>[NH4+:1].[OH-:26].[Cl:20][C:13]1[CH:12]=[C:11]2[C:16]([C:17]([C:18]#[N:19])=[C:9]([C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:25]([NH:24][CH2:22][CH3:23])=[O:26])[CH:8]=[N:7][CH:6]=3)[N:10]2[CH3:21])=[CH:15][CH:14]=1

Participants

5

Reactant 2

HCID 8022Ethyl isocyanateHCID 58215751HCID 58215751, compound

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 58215550HCID 58215550, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-aminomethyl-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile (Example 186e, 0.100 g, 0.337 mmol) in dichloromethane (3 mL) is added ethyl isocyanate (0.030 g, 0.422 mmol) and the reaction is stirred at room temperature for 45 min. The mixture is then washed with water and extracted with dichloromethane twice. The organic phase is concentrated in vacuo to give a residue which is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 1-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-3-ethyl-urea as a solid. 1H NMR (400 MHz, MeOD) δ ppm 1.14 (t, J=7.2 Hz, 3H), 3.20 (q, J=7.3 Hz, 2H), 3.82 (s, 3H), 4.52 (s, 2H), 7.38 (dd, J=8.3, 1.8 Hz, 1H), 7.71 (d, J=8.6 Hz, 1H), 7.76 (d, J=1.5 Hz, 1H), 8.08 (t, J=2.1 Hz, 1H), 8.73 (d, J=2.0 Hz, 1H), 8.76 (d, J=2.3 Hz, 1H). HRMS (ESI) m/z 368.1275 [(M+H)+ Calcd for C19H19ClN5O: 368.1278].

Workup

  1. washThe mixture is then washed with water
  2. extractionextracted with dichloromethane twice
  3. concentrationThe organic phase is concentrated in vacuo
  4. customto give a residue which
  5. customis purified by reverse phase HPLC with Xbridge Shield RP18 column

Sources & evidence

ORD record
ord-80bac5721c1f479faa08a1325e1bbfe9
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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