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Acetic Anhydride → N-acetyl-N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide

HRID 1517079
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HRID 1517079 반응식
[NH2:1][C:2]1[N:7]=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.CCN([CH2:37][CH3:38])CC.[C:39](OC(=O)C)(=[O:41])[CH3:40].C(=O)([O-])[O-:47].[Na+].[Na+]>CC(C)=O>[CH3:21][C:5]1[CH:4]=[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[C:2]([NH:1][C:39](=[O:41])[CH3:40])=[N:7][C:6]=1[C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)[CH2:12][CH2:11]1)=[O:9].[C:39]([N:1]([C:2]1[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)=[CH:4][C:5]([CH3:21])=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[CH2:12][CH2:11]2)=[O:9])[N:7]=1)[C:37](=[O:47])[CH3:38])(=[O:41])[CH3:40]
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참가 물질

7

반응물 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 44547360[6-Amino-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

생성물 2

HCID 57441146N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide
HCID 58016733
N-acetyl-N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide
수율 37%

시약·촉매·용매 1

HCID 180Acetone용매

실험 절차

A solution of 0.22 g (0.5 mmol) of [6-amino-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 7) in 5 ml of acetone was treated with 0.35 ml=0.26 g (2.5 mmol) of Et3N, followed by 0.19 ml=0.21 g (2.0 mmol) of acetic anhydride and the reaction mixture was subsequently heated up to reflux. After 22 hours, it was poured into crashed ice, the pH was adjusted to 8-9 with sodium carbonate solution and it was extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 3:2) to give 0.12 g (51%) the N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide as light yellow solid [MS: 475.2 (MH+)] and 0.098 g (37%) of N-acetyl-N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide as yellow solid. MS: 517.2 (MH+).

후처리

  1. temperaturethe reaction mixture was subsequently heated up
  2. temperatureto reflux
  3. additionit was poured
  4. extractionwas extracted twice with EtOAc
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 3:2)

출처 및 근거

ORD 기록
ord-f81965d9ded34299a3923957732c3859
출처 데이터셋
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08227613B2

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