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

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).

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

ORDレコード

ord-a40e81804cd44e8ea34e3b9f56544123

出典データセット

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09242993B2