Dimethylformamide → Ammonium Hydroxide

HRID 593510Notes

Reaction equation

HRID 593510 reaction equation
Cl.[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.[H-].[Na+].Br[CH2:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=1[F:30].CN(C=[O:35])C>>[NH4+:5].[OH-:35].[F:30][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:22]=1[CH2:21][N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3]([CH3:2])=[C:4]1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:26]#[N:27]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 27831494-(Bromomethyl)-3-fluorobenzonitrileHCID 445539613-Methyl-2-(3-pyridyl)indole hydrochloride

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 670935093-Fluoro-4-(3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzonitrile

Procedure

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.080 g, 0.326 mmol) and DMF (1.5 mL), and 60% NaH in mineral oil (0.028 g, 0.719 mmol) is added. The mixture is stirred at room temperature for 20 min, followed by addition of 4-bromomethyl-3-fluoro-benzonitrile (0.175 g, 0.817 mmol). The reaction mixture stirred at room temperature for 30 min. The residue is diluted with DMF (1.5 mL), filtered and purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 3-fluoro-4-(3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzonitrile as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 2.32 (s, 3H), 5.47 (s, 2H), 6.62 (t, J=7.6 Hz, 1H), 7.20 (t, J=7.5 Hz, 1H), 7.27 (t, J=7.6 Hz, 1H), 7.38 (d, J=8.1 Hz, 2H), 7.50 (d, J=9.9 Hz, 1H), 7.56 (dd, J=7.8, 4.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.86 (dd, J=7.8, 1.8 Hz, 1H), 8.52 (s, 1H), 8.60 (dd, J=4.9, 1.6 Hz, 1H). HRMS (ESI) m/z 342.1394 [(M+H)+ Calcd for C22H17FN3: 342.1407].

Workup

  1. additionis added
  2. stirringThe reaction mixture stirred at room temperature for 30 min
  3. filtrationfiltered
  4. custompurified by reverse phase HPLC with Xbridge Shield RP18 column

Sources & evidence

ORD record
ord-c9dee8437e0d4ef3b2cde3c8e607e2fb
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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