Sodium hydride → tert-butyl trans-3-{[(2-chloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]methyl}-4-methylpyrrolidine-1-carboxylate

HRID 577672Notes

Reaction equation

HRID 577672 reaction equation
[OH:1][CH2:2][C@H:3]1[C@H:7]([CH3:8])[CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[H-].[Na+].[Cl:18][C:19]1[N:20]=[C:21](Cl)[C:22]2[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:23]=2[N:24]=1>CN(C=O)C>[Cl:18][C:19]1[N:20]=[C:21]([O:1][CH2:2][C@H:3]2[C@H:7]([CH3:8])[CH2:6][N:5]([C:9]([O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[O:10])[CH2:4]2)[C:22]2[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:23]=2[N:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 219764212,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidineHCID 56604180rac-tert-butyl (3R,4R)-3-(hydroxymethyl)-4-methylpyrrolidine-1-carboxylate

Product 1

HCID 86679617tert-butyl trans-3-{[(2-chloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]methyl}-4-methylpyrrolidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of tert-butyl trans-3-(hydroxymethyl)-4-methylpyrrolidine-1-carboxylate (0.58 g, 2.7 mmol) in DMF (15 mL) was added NaH (60% in oil, 162 mg, 4.05 mmol) at 0° C. After stirring at rt for 30 min, 2,4-dichloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.85 g, 2.7 mmol) was added to the mixture. The resulting mixture was stirred at rt for 1 hr. TLC (petroleum ether/EtOAc=5:1) showed the reaction was complete. The reaction mixture was quenched by water (10 mL) and extracted with EtOAc (two×20 mL). The combined organic layers were washed with brine (four×20 mL), dried over Na2SO4 and concentrated to yield the title compound (1.34 g, 100% yield) as a brown oil.

Workup

  1. stirringThe resulting mixture was stirred at rt for 1 hr
  2. customThe reaction mixture was quenched by water (10 mL)
  3. extractionextracted with EtOAc (two×20 mL)
  4. washThe combined organic layers were washed with brine (four×20 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c554ac82c04a4a36b47f659ec46ce48e
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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