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Triethylamine → 4-[3-(4-Tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

HRID 1432939
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HRID 1432939 반응식
[CH2:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C:5]1=[O:17])[CH:2]=[CH2:3].[C:18]([O:22][C:23](=[O:32])[NH:24][C:25]1[CH:30]=[CH:29][N:28]=[CH:27][C:26]=1I)([CH3:21])([CH3:20])[CH3:19].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(CC)CC>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:13]([O:12][C:10]([N:7]1[CH2:8][CH2:9][N:4]([CH:1]=[CH:2][CH2:3][C:30]2[CH:29]=[N:28][CH:27]=[CH:26][C:25]=2[NH:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:32])[C:5](=[O:17])[CH2:6]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]
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참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl esterHCID 544523841-(2-Propenyl)-4-tert-butyloxycarbonyl-2-piperazinone

생성물 1

HCID 538781434-[3-(4-Tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매
HCID 6344Dichloromethane용매

반응 조건

온도
100 °C

실험 절차

1-Allyl-4-(tert-butyloxycarbonyl)-piperazin-2-one (0.49 g, 2.0 mmol) is treated with (3-iodo-pyridin-4-yl)-carbamic acid tert-butyl ester (0.64 g, 2.0 mmol), Pd(OAc)2 (14 mg, 0.06 mmol), P(o-tol)3 (37 mg, 0.12 mmol), and Et3N (0.56 mmol) in a seal tube. The mixture is stirred at 100° C. overnight, then diluted with CH2Cl2 and washed H2O (2×). The CH2Cl2 layer is concentrated and the residue is chromatographed (5% MeOH/CH2Cl2) to give a mixture of two isomers (0.40 g, 0.92 mmol). The mixture is separated into its constituent isomers upon further chromatography (EtOAc) to give 4-[3-(4-tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (90 mg, 0.21 mmol, higher Rf value) and 4-[3-(4-tert-butoxycarbonylamino-pyridin-3-yl)-allyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester_(0.24 g, 0.56 mmol, lower Rf value). For the former: MS m/z 433 (M+1); 1H NMR (CDCl3, 300 MHz) δ8.38 (d, 1H), 8.28 (s, 1H), 7.93 (d, 1H), 7.48 (d, 1H), 6.67 (s, 1H), 5.10 (m, 1H), 4.15 (s, 2H), 3.70 (t, 2H), 3,46 (t, 2H), 3.39 (d, 2H), 1.48 (s, 9H), 1.45 (s, 9H). For the latter: MS m/z 433 (M+1); 1H NMR (CDCl3, 300 MHz) δ8.39 (s, 1H), 8.37 (d, 1H), 7.98 (d, 1H), 6.77 (s, 1H), 6.52 (d, 1H), 6.07 (m, 1H), 4.23 (d, 2H), 4.12 (s, 2H), 3,69 (t, 2H), 3.40 (t, 2H), 1.52 (s, 9H), 1.45 (s, 9H).

후처리

  1. washwashed H2O (2×)
  2. concentrationThe CH2Cl2 layer is concentrated
  3. customthe residue is chromatographed (5% MeOH/CH2Cl2)
  4. customto give
  5. additiona mixture of two isomers (0.40 g, 0.92 mmol)
  6. customThe mixture is separated into its constituent isomers upon further chromatography (EtOAc)

출처 및 근거

ORD 기록
ord-a4c2f43942d54d8287ef4ae1ebe664cd
출처 데이터셋
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07612075B2

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