Dimethylformamide → Ammonium Hydroxide

HRID 593541Notes

Reaction equation

HRID 593541 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[NH:4][C:3]=1[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.CN(C=[O:23])C.[H-].[Na+].Cl[CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31]>C(OCC)(=O)C>[NH4+:4].[OH-:23].[C:11]([C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C:3]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)=[C:2]2[CH3:1])#[N:12]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 445541323-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 582156002,2-Dimethyl-propionic acid 5-cyano-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 6, 0.200 g, 0.856 mmol) and DMF (10 mL). The mixture is cooled to 0° C. and 60% NaH in mineral oil (0.086 g, 2.14 mmol) is added. The mixture is stirred at room temperature for 20 min followed by addition of 2,2-dimethyl-propionic acid chloromethyl ester (0.310 mL, 2.14 mmol). After stirring at room temperature for 1.5 h, the mixture is diluted with ethyl acetate and washed with water. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 2,2-dimethyl-propionic acid 5-cyano-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl ester product as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 1.12 (s, 9H), 2.31 (s, 3H), 6.10 (s, 2H), 7.62 (dd, J=8.5, 1.6 Hz, 1H), 7.68 (ddd, J=7.9, 5.0, 0.8 Hz, 1H), 7.81 (d, J=8.6 Hz, 1H), 8.04 (dt, J=8.1, 2.0, 1.8 Hz, 1H), 8.09 (d, J=1.0 Hz, 1H), 8.66-8.76 (m, 2H). HRMS (ESI) m/z 348.1700 [(M+H)+ Calcd for C21H22N3O2: 348.1712].

Workup

  1. stirringAfter stirring at room temperature for 1.5 h
  2. washwashed with water
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by reverse phase HPLC with Xbridge Shield RP18 column

Sources & evidence

ORD record
ord-246dcfb8cfc547d38ee0924765496beb
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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