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 448718Notes

Reaction equation

HRID 448718 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-b92a133b4e774541b41030584a032059
Source dataset
uspto-grants-2013_07
Patent number
US08481712B2

Reaction notes

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