Methyl iodide → 2-chloro-5,7,7-trimethyl-4-((S)-3-methylmorpholino)-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide

HRID 595074Notes

Reaction equation

HRID 595074 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[Cl:9][C:10]1[N:11]=[C:12]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[CH3:29])[C:13]2[CH2:18][S:17](=[O:20])(=[O:19])[C:16]([CH3:22])([CH3:21])[C:14]=2[N:15]=1.CI>C1COCC1>[Cl:9][C:10]1[N:11]=[C:12]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[CH3:29])[C:13]2[CH:18]([CH3:2])[S:17](=[O:19])(=[O:20])[C:16]([CH3:21])([CH3:22])[C:14]=2[N:15]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 89487214(S)-2-chloro-7,7-dimethyl-4-(3-methylmorpholino)-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide

Product 1

HCID 894874572-chloro-5,7,7-trimethyl-4-((S)-3-methylmorpholino)-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxideYield 77.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LDA (2.5 mL, 5 mmol) was added dropwise to a solution of (S)-2-chloro-7,7-dimethyl-4-(3-methylmorpholino)-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide (Step vi, 1.5 g, 4.5 mmol) in THF (30 mL) at −78° C. The mixture was stirred at this temperature for 0.5 h, MeI (0.7 g, 5 mmol) in THF (5 mL) was added dropwise to the above mixture. The resulted mixture was stirred at room temperature for 2 h. Then the mixture was poured into sat.NH4Cl, extracted with EtOAc (3×30 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography to give 2-chloro-5,7,7-trimethyl-4-((S)-3-methylmorpholino)-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide (1.2 g, yield 77%) as a yellow solid. 1H NMR (400 MHz, CDCl3) 1.38-4.31 (m, 1H), 4.29-4.21 (m, 1H), 3.99-3.96 (m, 1H), 3.78-3.43 (m, 5H), 1.65-1.25 (m, 12H).

Workup

  1. stirringThe resulted mixture was stirred at room temperature for 2 h
  2. additionThen the mixture was poured
  3. extractionNH4Cl, extracted with EtOAc (3×30 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a40e81804cd44e8ea34e3b9f56544123
Source dataset
uspto-grants-2016_01
Patent number
US09242993B2

Reaction notes

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