Hydrochloric Acid → 4-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidine

HRID 334226Notes

Reaction equation

HRID 334226 reaction equation
C(OC([N:6]1[CH:10]=[C:9]([C:11]2[C:12]3[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:13]=3[N:14]=[CH:15][N:16]=2)[CH:8]=[N:7]1)C)C.O1CCCC1.Cl.[OH-].[Na+]>O>[NH:6]1[CH:10]=[C:9]([C:11]2[C:12]3[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:13]=3[N:14]=[CH:15][N:16]=2)[CH:8]=[N:7]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 578688444-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a reactor equipped with overhead stirring, condenser, thermowell, and nitrogen inlet was charged crude 4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (15, 1030.9 g based on 100% conversion, 2.66 mol), tetrahydrofuran (THF, 0.9 L), water (H2O, 4.4 L), and a 10% aqueous HCl solution (2.7 L, 10.64 mol, 3.44 equiv) at room temperature. The resulting reaction mixture was stirred at room temperature for 2-5 h. When the reaction was deemed complete by HPLC analysis, the reaction mixture was treated with a 30% aqueous sodium hydroxide (NaOH) solution (940 mL, 11.70 mol, 3.78 equiv) at room temperature. The resulting reaction mixture was stirred at room temperature for 1-2 h. The solids were collected by filtration, washed with water (2×0.75 L), and dried in a vacuum oven at 45-55° C. to constant weight to afford the crude 4-(1H-pyrazol-4-yl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine (5, 826.8 g, 839.1 g theoretical, 98.5% yield) as off-white solids (94.2 area % pure by HPLC). This crude material was subsequently recrystallized in acetonitrile to afford pure compound 5 (738.4 g, 839.1 g theoretical, 88% yield) as white crystals (99.5 area % by HPLC), which was found to be identical in every comparable aspect to the material made from Method A.

Workup

  1. customTo a reactor equipped with overhead stirring, condenser
  2. customat room temperature
  3. customThe resulting reaction mixture
  4. customThe resulting reaction mixture
  5. stirringwas stirred at room temperature for 1-2 h
  6. filtrationThe solids were collected by filtration
  7. washwashed with water (2×0.75 L)
  8. customdried in a vacuum oven at 45-55° C. to constant weight
  9. customto afford the crude 4-(1H-pyrazol-4-yl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine (5, 826.8 g, 839.1 g theoretical, 98.5% yield) as off-white solids (94.2 area % pure by HPLC)
  10. customThis crude material was subsequently recrystallized in acetonitrile

Sources & evidence

ORD record
ord-f530e6b3d4a04459aa897aef9d85a6b8
Source dataset
uspto-grants-2014_11
Patent number
US08883806B2

Reaction notes

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