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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Sulfuric Acid → N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(3-methyl-1,2-oxazol-5-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 68417
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HRID 68417 반응식
[CH3:1][C:2](=[N:4][OH:5])[CH3:3].C([Li])CCC.[C:11]([NH:19][C:20]1[S:21][CH2:22][C@@H:23]2[CH2:29][C@H:28]([C:30](OC)=O)[O:27][CH2:26][C@:24]2([C:34]2[CH:39]=[C:38]([Br:40])[CH:37]=[CH:36][C:35]=2[F:41])[N:25]=1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.S(=O)(=O)(O)O.[OH-].[Na+]>O1CCCC1>[Br:40][C:38]1[CH:37]=[CH:36][C:35]([F:41])=[C:34]([C@:24]23[CH2:26][O:27][C@@H:28]([C:30]4[O:5][N:4]=[C:2]([CH3:3])[CH:1]=4)[CH2:29][C@H:23]2[CH2:22][S:21][C:20]([NH:19][C:11](=[O:18])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[N:25]3)[CH:39]=1
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참가 물질

7

반응물 5

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 67180Acetone, oximeHCID 86762655methyl (4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 86762654
N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(3-methyl-1,2-oxazol-5-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of propan-2-one oxime (0.216 g, 2.96 mmol) in tetrahydrofuran (10 mL) was cooled to 0° C. To this solution was added n-butyllithium (2.5 M in hexanes, 2.40 mL, 6.00 mmol) in a drop-wise manner. The resulting solution was allowed to warm to room temperature and left stirring at room temperature for 25 minutes. The resulting solution was cooled again to 0° C., followed by a drop-wise addition of methyl (4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylate (C35) (1.09 g, 2.03 mmol) in tetrahydrofuran (3 mL). The reaction mixture was allowed to warm to room temperature and was left stirring for 25 minutes. The reaction mixture was cooled to 0° C. again, and sulfuric acid (0.840 mL, 15.8 mmol) was added in a drop-wise manner. The reaction mixture was allowed to warm up to room temperature and was left stirring for 16 hours at room temperature. The reaction mixture was basified to pH 12 with sodium hydroxide (5 N, ˜4 mL) and then extracted with ethyl acetate (3×100 mL). The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure to give an oily residue. Purification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) afforded the product as a white solid. Yield: 330 mg, 63%. LCMS m/z 532.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.12 (br s, 1H), 7.47-7.61 (m, 4H), 7.19 (dd, J=12.0, 8.9 Hz, 1H), 4.97 (br d, J=9.4 Hz, 1H), 4.31 (dd, J=11.8, 1.5 Hz, 1H), 4.00-4.14 (m, 2H), 3.00 (dd, J=13.2, 4.0 Hz, 1H), 2.83 (dd, J=13.1, 2.9 Hz, 1H), 2.10 (d, J=12.1 Hz, 1H).

후처리

  1. waitleft
  2. temperatureThe resulting solution was cooled again to 0° C.
  3. temperatureto warm to room temperature
  4. waitwas left
  5. stirringstirring for 25 minutes
  6. temperatureThe reaction mixture was cooled to 0° C. again
  7. temperatureto warm up to room temperature
  8. waitwas left
  9. stirringstirring for 16 hours at room temperature
  10. extractionextracted with ethyl acetate (3×100 mL)
  11. dry with materialThe combined organics were dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto give an oily residue
  15. customPurification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-7b1a46e16a564111947ce32e2155ed84
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08822456B2

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