Sodium hydride → 6-Nitro-1-pyrimidin-5-ylmethyl-1H-indole

HRID 1713409Notes

Reaction equation

HRID 1713409 reaction equation
O[CH2:2][C:3]1[CH:4]=[N:5][CH:6]=[N:7][CH:8]=1.CS(Cl)(=O)=O.[N+:14]([C:17]1[CH:25]=[C:24]2[C:20]([CH:21]=[CH:22][NH:23]2)=[CH:19][CH:18]=1)([O-:16])=[O:15].N1C2C(=CC=CC=2)C=C1.[H-].[Na+].S([O-])(=O)(=O)C>C(Cl)Cl.CN(C=O)C>[N+:14]([C:17]1[CH:25]=[C:24]2[C:20]([CH:21]=[CH:22][N:23]2[CH2:2][C:3]2[CH:4]=[N:5][CH:6]=[N:7][CH:8]=2)=[CH:19][CH:18]=1)([O-:16])=[O:15]

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 15466386(Pyrimidin-5-yl)methanolHCID 667756606-Nitroindole 1H-indole

Product 1

HCID 667755866-Nitro-1-pyrimidin-5-ylmethyl-1H-indoleYield 39%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

5-(Hydroxymethyl)pyrimidine (16.2 g, 147 mmol) was dissolved in 500 mL of CH2Cl2 and cooled to −40° C. MsCl (16.0 g, 140 mmol) was added at 40° C. The mixture was stirred for 1 hour allowing to reach −20° C. The solution was used as such. 6-Nitroindole-1H-indole (35.6 g, 220 mmol) was dissolved in 750 mL of DMF and NaH (50%, 12 g, 250 mmol) was added in portions and the mixture was stirred for 1 hour. The mixture was cooled to −40° C. and the solution of the mesylate was added dropwise. The mixture was allowed to reach room temperature overnight. The mixture was quenched with water and extracted with ethyl acetate (2×). The combined organic layers were washed with water (2×) and brine and dried over Na2SO4. After concentration in vacuo the material was purified by means of column chromatography (silica, heptane/ethyl acetate (1:1)→(1:4)) affording compound the title compound as a yellow solid (14 g, 55 mmol, 39%).

Workup

  1. customto reach −20° C
  2. stirringthe mixture was stirred for 1 hour
  3. temperatureThe mixture was cooled to −40° C.
  4. waitto reach room temperature overnight
  5. customThe mixture was quenched with water
  6. extractionextracted with ethyl acetate (2×)
  7. washThe combined organic layers were washed with water (2×) and brine
  8. dry with materialdried over Na2SO4
  9. concentrationAfter concentration in vacuo the material
  10. customwas purified by means of column chromatography (silica, heptane/ethyl acetate (1:1)→(1:4))

Sources & evidence

ORD record
ord-dd2ccd01438d4e6eb419fa84bf42d3a9
Source dataset
uspto-grants-2010_09
Patent number
US07795280B2

Reaction notes

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