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

HRID 2252668Notes

Reaction equation

HRID 2252668 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.[NH2:32][C:33]1[N:34]=[C:35]([Cl:42])[C:36]2[CH:41]=[CH:40][NH:39][C:37]=2[N:38]=1.[OH-].[K+].COCCOCCN(CCOCCOC)CCOCCOC>C(Cl)Cl.C(#N)C>[NH2:32][C:33]1[N:34]=[C:35]([Cl:42])[C:36]2[CH:41]=[CH:40][N:39]([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:37]=2[N:38]=1

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 14797Potassium HydroxideHCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-HCID 53244134-chloro-7H-pyrrolo(2,3-d)pyrimidin-2-amineHCID 11283339Methyl 3,5-bis-O-((2,4-dichlorophenyl)methyl)-2-C-methyl-alpha-D-ribofuranoside

Product 1

HCID 112390772-Amino-4-chloro-7-[3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidineYield 40%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice-cold solution of the product from Step C of Example 2 (1.27 g, 2.57 mmol) in CH2Cl2 (30 mL) was added HBr (5.7 M in acetic acid; 3 mL) dropwise. The reaction mixture was stirred at room temperature for 2 h, concentrated under diminished pressure and coevaporated with toluene (2×15 mL). The resulting oil was dissolved in acetonitrile (MeCN) (15 mL) and added dropwise into a well-stirred mixture of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine [for preparation, see Heterocycles 35: 825 (1993)] (433 mg, 2.57 mmol), KOH (85%, powdered) (0.51 g, 7.7 mmol), tris-[2-(2-methoxyethoxy)ethyl]amine (165 μL, 0.51 mmol) in acetonitrile (30 mL). The resulting mixture was stirred at room temperature for 1 h, filtered and evaporated. The residue was purified on a silica gel column using hexanes/EtOAc, 5/1, 3/1 and 2/1, as eluent to give the title compound as a colorless foam (0.65 g).

Workup

  1. concentrationconcentrated under diminished pressure
  2. dissolutionThe resulting oil was dissolved in acetonitrile (MeCN) (15 mL)
  3. stirringThe resulting mixture was stirred at room temperature for 1 h
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-263dfb87c1514c86bebe1f71799cf901
Source dataset
uspto-grants-2008_01
Patent number
US07323453B2

Reaction notes

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