Hydrogen Bromide → 7-[3,5-Bis-O-[(2,4-dichlorophenyl)methyl]-2-C-methyl-beta-D-ribofuranosyl]-4-chloro-5-methyl-7H-pyrrolo[2,3-D]pyrimidine

HRID 448697Notes

Reaction equation

HRID 448697 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]=[C:42]([CH3:43])[C:35]=12.C(#N)C>C(Cl)Cl>[Cl:33][C:34]1[C:35]2[C:42]([CH3:43])=[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 178430152HCID 178430152, compound

Product 1

HCID 114222687-[3,5-Bis-O-[(2,4-dichlorophenyl)methyl]-2-C-methyl-beta-D-ribofuranosyl]-4-chloro-5-methyl-7H-pyrrolo[2,3-D]pyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of the product from Step C of Example 62 (1.06 g, 2.1 mmol) in CH2Cl2 (30 mL) was added HBr (5.7 M in acetic acid; 2.2 mL) dropwise. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature for 2 h, concentrated in vacuo and co-evaporated with toluene (2×15 mL). The resulting oil was dissolved in MeCN (10 mL) and added dropwise into a solution of the sodium salt of 4-chloro-5-methyl-1H-pyrrolo[2,3-d]pyrimidine in acetonitrile [generated in situ from 4-chloro-5-methyl-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see J. Med. Chem. 33: 1984 (1990)] (0.62 g, 3.7 mmol) in anhydrous acetonitrile (70 mL), and NaH (60% in mineral oil, 148 mg, 3.7 mmol), after 2 h of vigorous stirring at rt]. The combined mixture was stirred at rt for 24 h and then evaporated to dryness. The residue was suspended in water (100 mL) and extracted with EtOAc (250+100 mL). The combined extracts were washed with brine (50 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (5×5 cm) using hexane/ethyl acetate (9/1, 5/1, 3/1) gradient as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (0.87 g) as a colorless foam.

Workup

  1. waitat room temperature for 2 h
  2. concentrationconcentrated in vacuo and co-evaporated with toluene (2×15 mL)
  3. dissolutionThe resulting oil was dissolved in MeCN (10 mL)
  4. stirringThe combined mixture was stirred at rt for 24 h
  5. customevaporated to dryness
  6. extractionextracted with EtOAc (250+100 mL)
  7. washThe combined extracts were washed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified on a silica gel column (5×5 cm)
  12. additionFractions containing the product
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-12972793dd3c4a2499918c85ad56f6f0
Source dataset
uspto-grants-2013_07
Patent number
US08481712B2

Reaction notes

Loading…