Methanol → 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol

HRID 1972472노트

반응식

HRID 1972472 반응식
[N+](C1SC(S([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:20][N:19]=3)[C@@H:14]([CH2:34][N:35]3[CH:40]4[CH2:41][CH:42]([OH:44])[CH2:43][CH:36]3[CH2:37][O:38][CH2:39]4)[CH2:13]2)(=O)=O)=CC=1)([O-])=O.[N+](C1SC(S([N:56]2[CH2:61][CH2:60][N:59]([C:62]3[N:67]=[CH:66][C:65]([C:68]([OH:77])([C:73]([F:76])([F:75])[F:74])[C:69]([F:72])([F:71])[F:70])=[CH:64][N:63]=3)[C@@H:58]([CH2:78][N:79]3[CH:84]4[CH2:85][C:86](=[O:88])[CH2:87][CH:80]3[CH2:81][O:82][CH2:83]4)[CH2:57]2)(=O)=O)=CC=1)([O-])=O.[OH-].[K+].CO>O>[F:32][C:29]([F:30])([F:31])[C:24]([C:21]1[CH:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][NH:12][CH2:13][C@@H:14]2[CH2:34][N:35]2[CH:36]3[CH2:43][CH:42]([OH:44])[CH2:41][CH:40]2[CH2:39][O:38][CH2:37]3)=[N:23][CH:22]=1)([OH:33])[C:25]([F:26])([F:27])[F:28].[F:76][C:73]([F:74])([F:75])[C:68]([C:65]1[CH:64]=[N:63][C:62]([N:59]2[CH2:60][CH2:61][NH:56][CH2:57][C@@H:58]2[CH2:78][N:79]2[CH:80]3[CH2:87][C:86](=[O:88])[CH2:85][CH:84]2[CH2:83][O:82][CH2:81]3)=[N:67][CH:66]=1)([OH:77])[C:69]([F:70])([F:72])[F:71]

참가 물질

7

반응물 4

HCID 887MethanolHCID 14797Potassium HydroxideHCID 866703529-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-olHCID 866703539-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

생성물 2

HCID 866703549-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-olHCID 866703559-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A 25-mL round-bottomed flask was charged with a 1:1 mixture of 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (300 mg, 0.44 mmol, Example 98, Step 5), potassium hydroxide (749 mg, 13.34 mmol), MeOH (5 mL) and water (2 mL) and was stirred at room temperature for 30 min. The solvent was removed in vacuo and then diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The organic layers were dried (Na2SO4), filtered, and concentrated to give 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (215 mg) which were used without purification.

후처리

  1. customThe solvent was removed in vacuo
  2. additiondiluted with water (50 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bce106984a54402a80ef58ea7bb58892
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431563B2

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