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 448686Notes

Reaction equation

HRID 448686 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 product from Step C of Example 62 (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 in vacuo and co-evaporated with toluene (2×15 mL). The resulting oil was dissolved in 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 rt 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 in vacuo and co-evaporated with toluene (2×15 mL)
  2. dissolutionThe resulting oil was dissolved in MeCN (15 mL)
  3. stirringThe resulting mixture was stirred at rt for 1 h
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-6995ad4a8b6c45bea3f0d9800c19d563
Source dataset
uspto-grants-2013_07
Patent number
US08481712B2

Reaction notes

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