Sodium hydride → HCID 22466491, compound

HRID 1934452Notes

Reaction equation

HRID 1934452 reaction equation
[H-].[Na+].[CH3:3][S:4][C:5]1[NH:10][C:9]2=[N:11][C:12]([CH2:14][CH3:15])=[CH:13][C:8]2=[C:7]([Cl:16])[N:6]=1.[F:17][C:18]([F:28])([F:27])[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Br>O1CCCC1.C(Cl)Cl>[CH3:3][S:4][C:5]1[N:6]=[C:7]([Cl:16])[C:8]2[CH:13]=[C:12]([CH2:14][CH3:15])[N:11]([CH2:22][C:21]3[CH:24]=[CH:25][CH:26]=[C:19]([C:18]([F:17])([F:27])[F:28])[CH:20]=3)[C:9]=2[N:10]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 178435386HCID 178435386, compound

Product 1

HCID 22466491HCID 22466491, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 48 mg (2.00 mmol) of sodium hydride in 4.0 mL of tetrahydrofuran was added 227 mg (1.00 mmol) of 2-(methylthio)-4-chloro-6-ethyl-1H-pyrrolo[2,3-d]pyrimidine and 478 mg (2.00 mmol) of 3-(trifluoromethyl)benzyl bromide. The reaction was stirred at ambient temperature for 18 hours then diluted with 30 mL of methylene chloride and washed with 20 mL of saturated sodium bicarbonate solution. The organic phase was dried with sodium sulfate and concentrated. The crude product was purified by flash chromatography (25 g silica, methylene chloride-heptane gradient 1:1 to 100:0) to provide 320 mg (83%) of 2-(methylthio)-4-chloro-6-ethyl-7-[[3-(trifluoromethyl)-phenyl]methyl]-7H-pyrrolo[2,3-d]pyrimidine as a white solid. nmr (500 MHz, CDCl3) δ1.31 (t, J=7.3 Hz, 3H), 2.58 (s, 3H), 2.59 (q, J=7.3 Hz, 2H), 5.44 (s, 2H), 6.31 (s, 1H), 7.18 (d, J=7.8 Hz, 1H), 7.41 (t, J=7.8 Hz, 1H), 7.45 (s, 1H), 7.54 (d, J=7.8 Hz, 1H)

Workup

  1. washwashed with 20 mL of saturated sodium bicarbonate solution
  2. dry with materialThe organic phase was dried with sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (25 g silica, methylene chloride-heptane gradient 1:1 to 100:0)

Sources & evidence

ORD record
ord-517cf9dc153444f0b2b6bfd4bb597e61
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

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