Sodium hydride → HCID 14256770, compound

HRID 1199961Notes

Reaction equation

HRID 1199961 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[CH2:7][N:8]([CH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[C:9]1[N:14]=[CH:13][N:12]=[C:11]2[NH:15][N:16]=[CH:17][C:10]=12.C1(C)C=CC(S([O:35][CH2:36][CH:37]2[CH2:41]OC(C)(C)[O:38]2)(=O)=O)=CC=1>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[CH2:7][N:8]([CH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[C:9]1[N:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:41][CH:37]([OH:38])[CH2:36][OH:35])[N:16]=[CH:17][C:10]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2350972,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonateHCID 14256769HCID 14256769, compound2×

Product 1

HCID 14256770HCID 14256770, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
80 °C

Procedure

To a suspension of 1.5 g (30 mmole) 50% sodium hydride in 50 ml. N,N-dimethylformamide are added dropwise 9.6 g. (30 mmole) 4-[N-(3-chlorobenzyl)-cyclopentylamino]-1H-pyrazolo[3,4-d]pyrimidine (compound of Example 1) in 25 ml. N,N-dimethylformamide. The reaction mixture is stirred for 1 hour at 80° C., 10.0 g. (35 mmole) 4-(4-toluenesulphonyloxymethyl)-2,2-dimethyl-1,3-dioxolan in 25 ml. N,N-dimethylformamide are added thereto, the reaction mixture is further stirred for 3 hours at 80° C. and evaporated in a vacuum. The residue is taken up in water, extracted with dichloromethane and the extract evaporated. The residue is mixed with 300 ml. 0.1N hydrochloric acid, heated under reflux for 10 hours, allowed to cool, washed with diethyl ether and the aqueous phase rendered alkaline with aqueous sodium hydroxide solution. After extraction with dichloromethane and evaporation of the extract, there are obtained 8.2 g. of crude product which is purified by chromatography on silica gel (elution agent: dichloromethane/methanol; 9:1 v/v). 4.1 g. (34% of theory) of the title compound are eluted which, after trituration with diethyl ether, melts at 98°-100° C.

Workup

  1. stirringthe reaction mixture is further stirred for 3 hours at 80° C.
  2. customevaporated in a vacuum
  3. extractionextracted with dichloromethane
  4. customthe extract evaporated
  5. additionThe residue is mixed with 300 ml
  6. temperature0.1N hydrochloric acid, heated
  7. temperatureunder reflux for 10 hours
  8. temperatureto cool
  9. washwashed with diethyl ether
  10. extractionAfter extraction
  11. customwith dichloromethane and evaporation of the extract, there
  12. customare obtained 8.2 g
  13. customof crude product which is purified by chromatography on silica gel (elution agent: dichloromethane/methanol; 9:1 v/v)
  14. wash(34% of theory) of the title compound are eluted which

Sources & evidence

ORD record
ord-5fd0820785c1443983a7e03d6fa14468
Source dataset
uspto-grants-1990_02
Patent number
US04904666

Reaction notes

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