Tetrahydrofuran → HCID 86696591, compound

HRID 2276329Notes

Reaction equation

HRID 2276329 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]3[C:14]([CH:13]=[CH:12][CH:11]=[CH:10]3)=[C:6]2[N:5]=[C:4]([CH3:15])[C:3]=1[CH2:16][C:17]([O:19][CH3:20])=[O:18].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O1C[CH2:34][CH2:33][CH2:32]1.ICCC>CN(C=O)C>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]3[C:14]([CH:13]=[CH:12][CH:11]=[CH:10]3)=[C:6]2[N:5]=[C:4]([CH3:15])[C:3]=1[CH:16]([CH2:32][CH2:33][CH3:34])[C:17]([O:19][CH3:20])=[O:18]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 336431-IodopropaneHCID 2733832Lithium HexamethyldisilazideHCID 86696590HCID 86696590, compound

Product 1

HCID 86696591HCID 86696591, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 2-(4-chloro-2-methylpyrimido[1,2-b]indazol-3-yl)acetate (0.289 g; 1 mmol) in dry DMF (4 mL) at −10° C. was slowly added a 1N solution of LHMDS in tetrahydrofuran (1.1 mL; 1.1 mmol). Then, 1-iodopropane (0.146 mL; 1.5 mmol) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was quenched by addition of a saturated solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (2-20%) in dichloromethane furnished 0.252 g (76%) of methyl 2-(4-chloro-2-methylpyrimido[1,2-b]indazol-3-yl)pentanoate as an oil. ESI/APCI(+): 332-334 (M+H).

Workup

  1. customThe reaction mixture was quenched by addition of a saturated solution of ammonium chloride
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography on silica gel using a gradient of ethyl acetate (2-20%) in dichloromethane

Sources & evidence

ORD record
ord-0ceef5eb536040e29270a20e9170f534
Source dataset
uspto-grants-2015_09
Patent number
US09132129B2

Reaction notes

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