Oxazole → (8R)-8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1,3-oxazol-2-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1424132노트

반응식

HRID 1424132 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C@:19]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[O:31]1[CH:35]=[CH:34][N:33]=[CH:32]1.CC(C)([O-])C.[Li+].[Cl-].[NH4+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:24]([O:23][CH2:22][C@:19]1([CH3:21])[S:18][CH2:17][CH2:16][N:15]2[C:11]([C:8]3([C:5]4[CH:6]=[CH:7][C:2]([C:32]5[O:31][CH:35]=[CH:34][N:33]=5)=[CH:3][CH:4]=4)[CH2:10][CH2:9]3)=[N:12][N:13]=[C:14]2[CH2:20]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

참가 물질

7

반응물 4

HCID 9255OxazoleHCID 25517Ammonium ChlorideHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86712920(8R)-3-[1-(4-Bromophenyl)cyclopropyl]-8-({[t-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

생성물 1

HCID 86712977(8R)-8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1,3-oxazol-2-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine수율 86.4%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

A solution of the compound (800 mg, 1.57 mmol) obtained in Example 52-1), oxazole (217 mg, 3.15 mmol), tetrakis(triphenylphosphine)palladium(0) (91 mg, 0.08 mmol), and lithium tert-butoxide (260 mg, 3.15 mmol) in dioxane (12 mL) was stirred for 2 h with heating to reflux. The reaction mixture was cooled to room temperature, saturated aqueous ammonium chloride (50 mL) was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate:methanol=70:30) to obtain the title compound (674 mg, 86%) in a yellow oily form.

후처리

  1. temperaturewith heating to reflux
  2. extractionthe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with saturated sodium chloride solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. concentrationAfter concentration under reduced pressure
  6. customthe residue was purified by silica gel chromatography (ethyl acetate:methanol=70:30)

출처 및 근거

ORD 기록
ord-90690672e5da4d89ae53f24552eeb808
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927536B2

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