Acetamide, N-methoxy-2-[(4-methoxyphenyl)methoxy]-N-methyl- → 2-[(4-Methoxybenzyl)oxy]-1-[5-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]ethanone

HRID 44942Notes

Reaction equation

HRID 44942 reaction equation
[S:1]1[C:5]([C:6]2[C:7]3[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=3[N:9]=[CH:10][N:11]=2)=[CH:4][N:3]=[CH:2]1.C([Li])CCC.CON(C)[C:31](=[O:43])[CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=1>C1COCC1.CCCCCC>[CH3:42][O:41][C:38]1[CH:39]=[CH:40][C:35]([CH2:34][O:33][CH2:32][C:31]([C:2]2[S:1][C:5]([C:6]3[C:7]4[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=4[N:9]=[CH:10][N:11]=3)=[CH:4][N:3]=2)=[O:43])=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 11424955Acetamide, N-methoxy-2-[(4-methoxyphenyl)methoxy]-N-methyl-HCID 574776204-(1,3-thiazol-5-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 574776382-[(4-Methoxybenzyl)oxy]-1-[5-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]ethanoneYield 66.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 4-(1,3-thiazol-5-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidine (2.12 g, 6.38 mmol) in THF (70 mL) at −78° C. was added 2.5 M n-butyllithium in hexane (3.06 mL) slowly dropwise. After stirring for 30 minutes, N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methylacetamide (2.29 g, 9.56 mmol) was added. The reaction was continued for 30 minutes following the addition, at −78° C., then the cooling bath was removed and the reaction was quenched with saturated ammonium chloride and extracted with ether. The extracts were dried with sodium sulfate and concentrated in vacuo. The crude mixture was purified by flash column chromatography (ethyl acetate/hexanes) to afford desired product (2.16 g, 66%).

Workup

  1. waitThe reaction was continued for 30 minutes
  2. additionthe addition
  3. customat −78° C., then the cooling bath was removed
  4. customthe reaction was quenched with saturated ammonium chloride
  5. extractionextracted with ether
  6. dry with materialThe extracts were dried with sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude mixture was purified by flash column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cac80054aafd425fb6a48ec705e88503
Source dataset
uspto-grants-2013_09
Patent number
US08541425B2

Reaction notes

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