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Triethylamine → 3-{5-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl]-1H-tetrazol-1-yl}-5-(trifluoromethyl)benzonitrile

HRID 517786
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HRID 517786 반응식
[C@H:1]12[CH2:26][C@H:4]([N:5]([CH2:7][C:8]3[N:12]([C:13]4[CH:14]=[C:15]([CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=4)[C:16]([NH2:18])=O)[N:11]=[N:10][N:9]=3)[CH2:6]1)[CH2:3][O:2]2.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>ClCCl>[C@H:1]12[CH2:26][C@H:4]([N:5]([CH2:7][C:8]3[N:12]([C:13]4[CH:14]=[C:15]([CH:19]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:21]=4)[C:16]#[N:18])[N:11]=[N:10][N:9]=3)[CH2:6]1)[CH2:3][O:2]2
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydride2회HCID 66656200HCID 66656200, 화합물2회

생성물 1

HCID 866919003-{5-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl]-1H-tetrazol-1-yl}-5-(trifluoromethyl)benzonitrile수율 37.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-{5-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl]-1H-tetrazol-1-yl}-5-(trifluoromethyl)benzamide (Intermediate 32, 100 mg, 0.272 mmol) and triethylamine (0.076 ml, 0.543 mmol) in dichloromethane (5 ml) was added trifluoroacetic anhydride (0.038 ml, 0.272 mmol). The reaction was stirred at room temperature for 4 hours before the addition of trifluoroacetic anhydride (0.038 ml, 0.272 mmol). The reaction was stirred at room temperature for a further three hours. The reaction was partitioned between DCM (5 mL) and water (5 mL). The organic layer was collected via a hydrophobic frit and the solvent removed. The residue was purified by silica chromatography (Biotage SP4, eluting a gradient from 20-80% EtOAc in iso-hexane). The compound was further purified by high pH MDAP to yield the title compound as a white solid (36 mg)

후처리

  1. customThe reaction was partitioned between DCM (5 mL) and water (5 mL)
  2. customThe organic layer was collected via a hydrophobic frit
  3. customthe solvent removed
  4. customThe residue was purified by silica chromatography (Biotage SP4
  5. washeluting a gradient from 20-80% EtOAc in iso-hexane)
  6. customThe compound was further purified by high pH

출처 및 근거

ORD 기록
ord-ee179f7ca84a4347896763ac94b9dc72
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09115132B2

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