Hexamethyldisilazane → HCID 131727138, compound

HRID 2118087Notes

Reaction equation

HRID 2118087 reaction equation
C(O[CH:5]1[CH2:9][O:8][C@@H:7]([CH2:10][O:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:6]1)(=O)C.[Si](I)(C)(C)C.C[Si](N[Si](C)(C)C)(C)C.[NH2:34][C:35]1[N:43]=[C:42]2[C:38]([NH:39][CH:40]=[N:41]2)=[C:37]([NH:44][CH:45]2[CH2:47][CH2:46]2)[N:36]=1.C(=O)(O)[O-].[Na+]>ClC(Cl)C>[C:12]([OH:19])(=[O:11])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[NH2:34][C:35]1[N:43]=[C:42]2[C:38]([N:39]=[CH:40][N:41]2[CH:5]2[CH2:9][O:8][C@@H:7]([CH2:10][O:11][C:12](=[O:19])[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[O:6]2)=[C:37]([NH:44][CH:45]2[CH2:47][CH2:46]2)[N:36]=1.[CH:13]1([NH:34][C:35]2[N:43]=[C:42]3[C:38]([NH:39][CH:40]=[N:41]3)=[CH:37][N:36]=2)[CH2:12][CH2:18]1

Participants

7

Reactant 5

HCID 13838HexamethyldisilazaneHCID 85247Trimethylsilyl iodideHCID 516892Sodium BicarbonateHCID 98154882-Amino-6-cyclopropylaminopurineHCID 11334608HCID 11334608, compound

Product 1

HCID 131727138HCID 131727138, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of of benzoic acid 4-acetoxy-[1,3]dioxolan-2(R)-ylmethyl ester (6.02 g, 18.8 mm) in dichloroethane (56 mL) was charged TMSI (3.2 mL) at −15° C. After the addition the reaction was stirred for 2 hours at −15° C. HMDS (5.9 mL, 28.2 mm) was added followed by 2-amino-6-cyclopropylaminopurine (3.57 g, 18.8 mm). The reaction was allowed to warm up to room temperature and was stirred for 48 hours followed by 3 hours of reflux. The reaction was cooled to room temperature and poured into saturated sodium bicarbonate solution. The mixture was filtered through a pad of Celite and the organic layer was separated. The aqueous layer was back-extracted with dichloromethane (2×20 mL). The combined organic phases were dried over sodium sulfate and concentrated to a residue. The crude product was purified by flash chromatography (40/60:EtOAc/Hexane followed by DCM/MeOH:25/1) to produce benzoic acid 4(R,S)-(2-amino-6-cyclopropylamino-purin-9-yl)-[1,3]dioxolan-2(R)-ylmethyl ester benzoate-cyclopropylaminopurine (2.25 g, 27% yield, cis/trans:1/1.25).

Workup

  1. additionAfter the addition the reaction
  2. temperatureto warm up to room temperature
  3. stirringwas stirred for 48 hours
  4. waitfollowed by 3 hours
  5. temperatureof reflux
  6. temperatureThe reaction was cooled to room temperature
  7. filtrationThe mixture was filtered through a pad of Celite
  8. customthe organic layer was separated
  9. extractionThe aqueous layer was back-extracted with dichloromethane (2×20 mL)
  10. dry with materialThe combined organic phases were dried over sodium sulfate
  11. concentrationconcentrated to a residue
  12. customThe crude product was purified by flash chromatography (40/60:EtOAc/Hexane followed by DCM/MeOH:25/1)

Sources & evidence

ORD record
ord-a0e4efc892334808b9e98fd6fec4948d
Source dataset
uspto-grants-2008_10
Patent number
US07442813B2

Reaction notes

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