Water → (4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(1-methyl-1H-pyrazol-4-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine

HRID 1496770노트

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HRID 1496770 반응식
[CH3:1][NH:2][NH2:3].O.[Br:5][C:6]1[CH:7]=[CH:8][C:9]([F:42])=[C:10]([C@:12]23[CH2:21][O:20][C@@H:19]([CH:22]([CH:28](OC)OC)[CH:23](OC)OC)[CH2:18][C@H:17]2[CH2:16][S:15][C:14]([NH:33]C(=O)C2C=CC=CC=2)=[N:13]3)[CH:11]=1.S(=O)(=O)(O)O>C(O)C>[Br:5][C:6]1[CH:7]=[CH:8][C:9]([F:42])=[C:10]([C@:12]23[CH2:21][O:20][C@@H:19]([C:22]4[CH:23]=[N:3][N:2]([CH3:1])[CH:28]=4)[CH2:18][C@H:17]2[CH2:16][S:15][C:14]([NH2:33])=[N:13]3)[CH:11]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 6061MethylhydrazineHCID 86762663N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(1,1,3,3-tetramethoxypropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 86762664(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(1-methyl-1H-pyrazol-4-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
60 °C

실험 절차

Methylhydrazine (0.0834 mL, 1.60 mmol) followed by water (2.2 mL) was added to a solution of N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(1,1,3,3-tetramethoxypropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C44) (0.65 g, 1.06 mmol) in ethanol (5 mL). Sulfuric acid (0.110 mL, 2.07 mmol) was then added in a drop-wise manner to the reaction mixture. The resulting solution was heated to 60° C. for 16 hours. The reaction mixture was partitioned between ethyl acetate (100 mL) and a saturated aqueous solution of sodium bicarbonate (100 mL). The layers were separated and the resulting aqueous layer was further extracted with ethyl acetate (3×100 mL). The combined organic layers were then dried over sodium sulfate, filtered and concentrated to give a mixture of product and benzoylated product (0.79 g), which was taken directly to the following step. LCMS m/z 427.1 [M+H+](product) and m/z 527.1 [M+H+](benzoylated product).

후처리

  1. customThe reaction mixture was partitioned between ethyl acetate (100 mL)
  2. customThe layers were separated
  3. extractionthe resulting aqueous layer was further extracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined organic layers were then dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give

출처 및 근거

ORD 기록
ord-5aed290876104148968032e7f6a2df53
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09198917B2

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