Hydrogen Bromide → 4-Amino-1-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-methyl-beta-d-ribofuranosyl]-1h-pyrazolo[3,4-d]pyrimidine

HRID 2212949Notes

Reaction equation

HRID 2212949 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:38]=[CH:37][N:36]=[C:35]2[NH:39][N:40]=[CH:41][C:34]=12.[H-].[Na+]>ClCCl.CN1CCCC1=O.C1(C)C=CC=CC=1>[NH2:32][C:33]1[N:38]=[CH:37][N:36]=[C:35]2[N:39]([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([CH3:30])[OH:29])[N:40]=[CH:41][C:34]=12

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 24758Sodium hydrideHCID 754201H-Pyrazolo[3,4-d]pyrimidin-4-amineHCID 11283339Methyl 3,5-bis-O-((2,4-dichlorophenyl)methyl)-2-C-methyl-alpha-D-ribofuranoside

Product 1

HCID 112963434-Amino-1-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-methyl-beta-d-ribofuranosyl]-1h-pyrazolo[3,4-d]pyrimidineYield 33%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To the compound from Step C of Example 62 (1.00 g, 2.02 mmol) in dichloromethane (20 mL) was bubbled HBr gas for 5 min until it was saturated. The resulting solution was stirred at room temperature for 10 min, evaporated in vacuo and coevaporated with anhydrous toluene (10 mL). 4-Amino-1H-pyrazolo[3,4-d]pyrimidine (Aldrich, 0.43 g, 3.18 mmol) and NaH (60%, 150 mg, 3.8 mmol) were stirred in 1-methyl-2-pyrrolidinone (10 mL) for 30 min. The resulting solution was poured into the above bromo sugar residue and the mixture was stirred overnight. The mixture was diluted with toluene (50 mL), washed with brine (10%, 3×50 mL) and concentrated under reduced pressure. The residue was chromatographed on silica gel (EtOAc as eluent) to afford a solid (400 mg).

Workup

  1. customevaporated in vacuo
  2. stirringthe mixture was stirred overnight
  3. washwashed with brine (10%, 3×50 mL)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on silica gel (EtOAc as eluent)

Sources & evidence

ORD record
ord-0b5f0555ae5a4f239109d97f8b62d35b
Source dataset
uspto-grants-2006_09
Patent number
US07105499B2

Reaction notes

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