Methyl iodide → 9-{[4-(Ethyloxy)phenyl]sulfonyl}-2,10a-dimethyl-8,9,10,10a-tetrahydropyrido[2',3':3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one

HRID 1427165Notes

Reaction equation

HRID 1427165 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:18][CH2:17][N:16]3[C:19](=[O:27])[C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[N:22][C:21]=4[CH:15]3[CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)[CH3:2].[Li+].[CH3:29][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:18][CH2:17][N:16]3[C:19](=[O:27])[C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[N:22][C:21]=4[C:15]3([CH3:29])[CH2:14]2)(=[O:11])=[O:12])=[CH:6][CH:5]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 575242899-{[4-(Ethyloxy)phenyl]sulfonyl}-2-methyl-8,9,10,10a-tetrahydropyrido[2',3':3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one

Product 1

HCID 575249189-{[4-(Ethyloxy)phenyl]sulfonyl}-2,10a-dimethyl-8,9,10,10a-tetrahydropyrido[2',3':3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 9-{[4-(ethyloxy)phenyl]sulfonyl}-2-methyl-8,9,10,10a-tetrahydropyrido[2′,3′:3,4]pyrrolo[1,2-a]pyrazin-5(7H)-one (31 mg) in dry THF (0.5 mL) under argon at −78° C. was added LiHMDS (0.104 mL, 1M, in THF) dropwise. The reaction was stirred at −78° C. for 30 minutes and then the temperature of the cool bath raised to −50° C. over 15 minutes. A solution of methyl iodide (75 μL) in dry THF (1 mL) was made and then 100 μL of this solution added to the reaction dropwise. The reaction was then allowed to warm to −10° C. naturally in the cool bath and then the cool bath removed and the reaction stirred for 20 minutes. LCMS showed good conversion to product. The reaction mixture was concentrated in vacuo and then the mixture taken up in 1:1 MeOH:DMSO and this mixture filtered before purification by MDAP to give the title compound (14 mg) as white solid.

Workup

  1. temperaturethe temperature of the cool bath raised to −50° C. over 15 minutes
  2. temperatureto warm to −10° C. naturally in the cool bath
  3. customthe cool bath removed
  4. stirringthe reaction stirred for 20 minutes
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. filtrationDMSO and this mixture filtered before purification by MDAP

Sources & evidence

ORD record
ord-0562a56f5c8a48bcb284431c6c47a051
Source dataset
uspto-grants-2015_01
Patent number
US08933132B2

Reaction notes

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