Sodium Hydroxide → 4-{(2R)-2-[({(2S)-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}benzoic Acid

HRID 47688노트

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HRID 47688 반응식
[CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][C@@H:11]2[CH2:13][O:12]2)=[CH:7][CH:6]=1.[NH2:16][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][CH:29]=3)[CH:24]=2)[O:19]1.[OH-].[Na+]>O1CCOCC1>[OH:12][C@H:11]([CH2:10][O:9][C:8]1[CH:14]=[CH:15][C:5]([CH2:4][CH2:3][O:2][CH3:1])=[CH:6][CH:7]=1)[CH2:13][NH:16][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][CH:37]=3)[CH:24]=2)[O:19]1

참가 물질

5

반응물 3

HCID 14798Sodium HydroxideHCID 9902206methyl 4-[(2R)-2-(aminomethyl)-3,4-dihydro-2H-chromen-6-yl]benzoateHCID 10976684(S)-3-[4-(2-Methoxyethyl)phenoxy]-1,2-epoxypropane

생성물 1

HCID 98702424-{(2R)-2-[({(2S)-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}benzoic Acid수율 10.5%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

To a solution of epoxide (Example 16, 0.25 mmol) in 2 mL of aqueous 1,4-dioxane (10% water) was added methyl 4-[(2R)-2-(aminomethyl)-3,4-dihydro-2H-chromen-6-yl]benzoate (40 mg, 0.13 mmol). The mixture was stirred at 80° C. for 72 hours and allowed to cool to room temperature. When ambient temperature was achieved, 1N aqueous sodium hydroxide (1 mL) was added to the solution at room temperature, and stirring continued for another 0.5 hour. The product was then purified by preparative HPLC (Gradient 0-70% Acetonitrile/0.1% aq. TFA) to obtain 6.7 mg of product (as a TFA salt). MH+492.4 (free base).

후처리

  1. temperatureto cool to room temperature
  2. customWhen ambient temperature
  3. stirringstirring
  4. waitcontinued for another 0.5 hour
  5. customThe product was then purified by preparative HPLC (Gradient 0-70% Acetonitrile/0.1% aq. TFA)

출처 및 근거

ORD 기록
ord-0846486d44fd4fddbad2b57d35bc9362
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06699860B2

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