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

HRID 2252667Notes

Reaction equation

HRID 2252667 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([CH2:30][CH3:31])[OH:29].Br.[Cl:33][C:34]1[N:39]=[CH:38][NH:37][C:36]2=[N:40][CH:41]=[CH:42][C:35]=12.[OH-].[K+].COCCOCCN(CCOCCOC)CCOCCOC.[Cl-].[NH4+]>ClCCl.C(#N)C.C(OCC)(=O)C>[Cl:33][C:34]1[C:35]2[CH:42]=[CH:41][N:40]([C@@H:13]3[O:16][C@H:17]([CH2:11][O:10][CH2:9][C:3]4[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=4[Cl:1])[C@@H:18]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=4[Cl:28])[C@@:12]3([CH2:30][CH3:31])[OH:29])[C:36]=2[N:37]=[CH:38][N:39]=1

Participants

10

Reactant 6

HCID 260Hydrogen BromideHCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-HCID 671439003,5-Bis-o-(2,4-dichlorophenylmethyl)-2-c-ethyl-1-o-methyl-alpha-d-ribofuranoseHCID 178418725HCID 178418725, compound

Product 1

HCID 872855044-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-ethyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidineYield 24.3%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the compound from Step A (1.02 mg, 2.0 mmol) in dichloromethane (40 mL) was added HBr (5.7 M in acetic acid) (1.75 mL, 10.0 mmol) dropwise at 0° C. The resulting solution was stirred at room temperature for 2 h, evaporated in vacuo and co-evaporated twice from toluene (10 mL). The oily residue was dissolved in acetonitrile (10 mL) and added to a vigorously stirred mixture of 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (307 mg, 2.0 mmol), potassium hydroxide (337 mg, 6.0 mmol) and tris[2-(2-methoxyethoxy)ethyl]amine (130 mg, 0.4 mmol) in acetonitrile (10 mL). The resulting mixture was stirred at room temperature overnight, and then poured into a stirred mixture of saturated ammonium chloride (100 mL) and ethyl acetate (100 mL). The organic layer was separated, washed with brine (100 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified on silica gel using ethyl acetate/hexane (1:2) as eluent to give the desired product (307 mg) as a colorless foam.

Workup

  1. customevaporated in vacuo
  2. dissolutionThe oily residue was dissolved in acetonitrile (10 mL)
  3. stirringThe resulting mixture was stirred at room temperature overnight
  4. customThe organic layer was separated
  5. washwashed with brine (100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified on silica gel

Sources & evidence

ORD record
ord-5e3a4c595dca4729ba7dfbe0c164fb74
Source dataset
uspto-grants-2008_01
Patent number
US07323453B2

Reaction notes

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