반응 #726262

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(1R)-2-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethanol

3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde

Na2SO4

NaBH4

→

title compound

수율 3.6%

6-({[((3S)-1-{(2R)-2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-2-hydroxyethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

수율 3.6%

용매

CH2Cl2

EtOH

반응 조건

후처리

1. 1
   workup.WAITAfter 2 h
2. 2
   기타the solution wa partitioned between ethyl acetate
3. 3
   농축concentrated
4. 4
   기타purified with column chromatography (silica, 0-8% MeOH in DCM (1% NH4OH))
5. 5
   기타affording a light yellow solid, which
6. 6
   기타was completed with chiral purification

실험 절차

To a stirred solution of (1R)-2-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethanol (90 mg, 0.28 mmol) in dry CH2Cl2 (2 mL) and dry EtOH (2 mL) was added 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (55 mg, 0.28 mmol) along with Na2SO4 (350 mg, 2.46 mmol). After 18 h at room temperature, NaBH4 (24 mg, 0.56 mmol) was added. After 2 h, the solution wa partitioned between ethyl acetate and the aqueous solution of sodium bicarbonate. The aqueous solution was extreacted several times with ethyl acetate. The organic fraction were pooled, concentrated and purified with column chromatography (silica, 0-8% MeOH in DCM (1% NH4OH)) affording a light yellow solid, which was completed with chiral purification. The title compound (5 mg, 3.6%) was provided as a white solid: LC/MS (ES) m/e 499 (M+H)+; 1H NMR (400 MHz, CD3OD): δ 8.56 (s, 1H), 8.14 (d, J=9.0 Hz, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.10 (d, J=9.2 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H), 5.82-5.84 (m, 1H), 4.03 (s, 3H), 3.64 (s, 2H), 3.39-3.41 (m, 1H), 3.09-3.12 (m, 1H), 2.87-3.07 (m, 2H), 2.59-2.67 (m, 2H), 2.48-2.52 (m, 2H), 2.28-2.36 (m, 2H), 1.86-1.97 (m, 1H), 1.37-1.46 (m, 1H), 1.16-1.18 (m, 1H).

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