Indole → 3-(2-Chloropyrimidin-4-yl)-1H-indole

HRID 1842784Notes

Reaction equation

HRID 1842784 reaction equation
C[Mg+].[Br-].[NH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5]1.[Cl:13][C:14]1[N:19]=[C:18](Cl)[CH:17]=[CH:16][N:15]=1>ClCCCl>[Cl:13][C:14]1[N:19]=[C:18]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[NH:4][CH:5]=2)[CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 798IndoleHCID 775312,4-DichloropyrimidineHCID 178418689HCID 178418689, compound

Product 1

HCID 597434283-(2-Chloropyrimidin-4-yl)-1H-indoleYield 46%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

CH3MgBr (3M in diethyl ether, 22.68 mL, 68.03 mmol) was added dropwise over a period of 10 minutes to a stirred solution of 1H-indole (7.97 g, 68.03 mmol) in 1,2-dichloroethane (250 mL) at 0° C. under an atmosphere of N2. The resulting solution was stirred for 15 minutes and then 2,4-dichloropyrimidine (15.00 g, 100.69 mmol) was added in one portion. The resulting solution was allowed to warm to r.t. and was stirred for a further 16 h. The reaction was quenched by the addition of CH3OH (25 mL) then the mixture was concentrated in vacuo and absorbed onto silica. Purification by FCC, eluting with 0-20% CH3OH in CH2Cl2 gave the title compound (7.17 g, 46%) as a yellow solid; 1H NMR: 7.20-7.28 (2H, m), 7.49-7.53 (1H, m), 7.91 (1H, d), 8.42 (1H, dd), 8.50 (1H, d), 8.53 (1H, d), 12.06 (1H, s); m/z: ES+ MH+ 230.

Workup

  1. stirringwas stirred for a further 16 h
  2. customThe reaction was quenched by the addition of CH3OH (25 mL)
  3. concentrationthe mixture was concentrated in vacuo
  4. customabsorbed onto silica
  5. customPurification by FCC
  6. washeluting with 0-20% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-bf2584565cb14744a0c80a9e841e9c7c
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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