Hydrogen Bromide → 4-Chloro-7-[3,5-bis-o-(2,4-dichlorobenzyl)-2-c-methyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

HRID 2252664Notes

Reaction equation

HRID 2252664 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C@@H:11]1[C@@H:17]([CH2:18][O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=2[Cl:28])[O:16][C@H:13](OC)[C@:12]1([CH3:30])[OH:29].Br.[Na].[Cl:33][C:34]1[N:39]=[CH:38][NH:37][C:36]2=[N:40][CH:41]=[CH:42][C:35]=12.C(#N)C>ClCCl>[Cl:33][C:34]1[C:35]2[CH:42]=[CH:41][N:40]([C@@H:13]3[O:16][C@H:17]([CH2:18][O:19][CH2:20][C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=4[Cl:28])[C@@H:11]([O:10][CH2:9][C:3]4[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=4[Cl:1])[C@@:12]3([CH3:30])[OH:29])[C:36]=2[N:37]=[CH:38][N:39]=1

Participants

7

Reactant 5

HCID 260Hydrogen BromideHCID 6342AcetonitrileHCID 5360545SodiumHCID 11283339Methyl 3,5-bis-O-((2,4-dichlorophenyl)methyl)-2-C-methyl-alpha-D-ribofuranosideHCID 178418725HCID 178418725, compound

Product 1

HCID 114449314-Chloro-7-[3,5-bis-o-(2,4-dichlorobenzyl)-2-c-methyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the compound from Step C (9.42 g, 19 mmol) in anhydrous dichloromethane (285 mL) at 0° C. was added HBr (5.7 M in acetic acid, 20 mL, 114 mmol) dropwise. The resulting solution was stirred at 0° C. for 1 h and then at room temperature for 3 h, evaporated in vacuo and co-evaporated with anhydrous toluene (3×40 mL). The oily residue was dissolved in anhydrous acetonitrile (50 mL) and added to a solution of the sodium salt of 4-chloro-1H-pyrrolo[2,3-d]pyrimidine in acetonitrile [generated in situ from 4-chloro-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see J. Chem. Soc., 131 (1960)] (8.76 g, 57 mmol) in anhydrous acetonitrile (1000 mL), and NaH (60% in mineral oil, 2.28 g, 57 mmol), after 4 h of vigorous stirring at room temperature]. The combined mixture was stirred at room temperature for 24 h, and then evaporated to dryness. The residue was suspended in water (250 mL) and extracted with EtOAc (2×500 mL). The combined extracts were washed with brine (300 mL, dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (10 cm×10 cm) using ethyl acetate/hexane (1:3 and 1:2) as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (5.05 g) as a colorless foam.

Workup

  1. waitat room temperature for 3 h
  2. customevaporated in vacuo and co-evaporated with anhydrous toluene (3×40 mL)
  3. dissolutionThe oily residue was dissolved in anhydrous acetonitrile (50 mL)
  4. stirringThe combined mixture was stirred at room temperature for 24 h
  5. customevaporated to dryness
  6. extractionextracted with EtOAc (2×500 mL)
  7. washThe combined extracts were washed with brine (300 mL
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified on a silica gel column (10 cm×10 cm)
  12. additionFractions containing the product
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-661aed51b23b4970a01e851217c1ac02
Source dataset
uspto-grants-2008_01
Patent number
US07323453B2

Reaction notes

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