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Triethylamine → 2-[1-(Biphenyl-4-carbonyl)-pyrrolidin-2-yl]-5-(4-tert-butoxycarbonylamino-pyridin-3-yl)-pent-4-ynoic acid methyl ester

HRID 901326
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HRID 901326 반응식
[CH3:1][O:2][C:3](=[O:27])[CH:4]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)=[O:14])[CH2:5][C:6]#[CH:7].[C:28]([O:32][C:33](=[O:42])[NH:34][C:35]1[CH:40]=[CH:39][N:38]=[CH:37][C:36]=1I)([CH3:31])([CH3:30])[CH3:29].C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I.CN(C=O)C>[CH3:1][O:2][C:3](=[O:27])[CH:4]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:19][CH:20]=1)=[O:14])[CH2:5][C:6]#[C:7][C:40]1[CH:39]=[N:38][CH:37]=[CH:36][C:35]=1[NH:34][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:42]
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참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl esterHCID 865880852-[1-(Biphenyl-4-carbonyl)-pyrrolidin-2-yl]-pent-4-ynoic acid methyl ester

생성물 1

HCID 692528602-[1-(Biphenyl-4-carbonyl)-pyrrolidin-2-yl]-5-(4-tert-butoxycarbonylamino-pyridin-3-yl)-pent-4-ynoic acid methyl ester

시약·촉매·용매 3

HCID 83717
Copper iodide
촉매
HCID 178418476HCID 178418476, 화합물촉매
HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

A flask is charged with 2-[1-(Biphenyl-4-carbonyl)-pyrrolidin-2-yl]-pent-4-ynoic acid methyl ester (0.58 g, 1.62 mmol), (3-iodopyridin-4-yl)-carbamic acid tert-butyl ester (0.52 g, 1.62 mmol), bis(triphenylphosphine)-palladium(II) chloride (0.057 g, 0.081 mmol), copper iodide (0.0104 g, 0.055 mmol), triethylamine (0.90 mL, 6.5 mmol) and DMF (7.3 mL) and heated at 90° C. for 2 h. The reaction is cooled to RT and partitioned between EtOAc (200 mL) and saturated sodium bicarbonate (75 mL). The organic layer is washed with saturated sodium bicarbonate (2×75 mL), brine (50 mL), dried over MgSO4 and concentrated. The residue is subjected to flash chromatography (1:1/EtOAc:hexanes) to give 2-[1-(biphenyl-4-carbonyl)-pyrrolidin-2-yl]-5-(4-tert-butoxycarbonylamino-pyridin-3-yl)-pent-4-ynoic acid methyl ester as an impure mixture (0.35 g, three components) which is used without further purification. This material (0.35 g, 0.63 mmol estimated), DBU (0.19 g, 1.26 mmol) and acetonitrile (7 mL) is stirred at 50° C. for 6 h. The reaction mixture is concentrated and purified by flash chromatography (0.5% MeOH/CH2Cl2) to (2.0% MeOH/CH2Cl2) to give the title compound (0.18 g, 0.325 mmol). 1H NMR (CDCl3, 300 MHz) 8.83(s, 1H), 8.41(m, 1H), 8.25(d, 1H), 7.65-7.53(m, 6H), 7.52-7.32(m, 3H), 6.80(s, 1H), 4.84-4.68(m, 1H), 3.73, 3.68(two s, 3H), 3.67-3.35(m, 6H), 2.21-1.91(m, 4H), 1.67(s, 9H).

후처리

  1. temperatureThe reaction is cooled to RT
  2. custompartitioned between EtOAc (200 mL) and saturated sodium bicarbonate (75 mL)
  3. washThe organic layer is washed with saturated sodium bicarbonate (2×75 mL), brine (50 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fff12119c10849d7b8861deadfd3a438
출처 데이터셋
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07361663B2

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