Hydrogen Bromide → 2-Amino-4-chloro-7-[3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-beta-D-ribofuranosy]-5-methyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 448693Notes

Reaction equation

HRID 448693 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].[NH2:33][C:34]1[NH:39][C:38]2=[N:40][CH:41]=[C:42]([CH3:43])[C:37]2=[C:36]([Cl:44])[N:35]=1.C(#N)C>C(Cl)Cl>[NH2:33][C:34]1[N:35]=[C:36]([Cl:44])[C:37]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:38]=2[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 178430157HCID 178430157, compound

Product 1

HCID 872855862-Amino-4-chloro-7-[3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-beta-D-ribofuranosy]-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 (1.57 g, 3.16 mmol) in CH2Cl2 (50 mL) was added HBr (5.7 M in acetic acid; 3.3 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 (2×20 mL). The resulting oil was dissolved in MeCN (20 mL) and added dropwise to a solution of the sodium salt of 2-amino-4-chloro-5-methyl-1H-pyrrolo[2,3-d]pyrimidine in acetonitrile [generated in situ from 2-amino-4-chloro-5-methyl-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see Liebigs Ann. Chem. 1984: 708-721] (1.13 g, 6.2 mmol) in anhydrous acetonitrile (150 mL), and NaH (60% in mineral oil, 248 mg, 6.2 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 (300+150 mL). The combined extracts were washed with brine (100 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (5×7 cm) using ethyl acetate/hexane (0 to 30% EtOAc in 5% step gradient) as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (0.96 g) as a colorless foam.

Workup

  1. waitat room temperature for 2 h
  2. concentrationconcentrated in vacuo and co-evaporated with toluene (2×20 mL)
  3. dissolutionThe resulting oil was dissolved in MeCN (20 mL)
  4. stirringThe combined mixture was stirred at rt for 24 h
  5. customevaporated to dryness
  6. extractionextracted with EtOAc (300+150 mL)
  7. washThe combined extracts were washed with brine (100 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified on a silica gel column (5×7 cm)
  12. additionFractions containing the product
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-a0be1ab3b4704d8383c97c22072aa156
Source dataset
uspto-grants-2013_07
Patent number
US08481712B2

Reaction notes

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