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Diisopropylethylamine → Methyl(1r,4s,5s,7s,10s)-4-benzyl-10-tert-butyl-5-hydroxy-1-[1-methyl-1-(methylsulfanyl)ethyl]-2,9,12-trioxo-7-[4-(2-pyridinyl)benzyl]-13-oxa-3,8,11-triazatetradec-1-ylcarbamate

HRID 1174177
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HRID 1174177 반응식
[NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@@H:3]([OH:32])[CH2:4][C@@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:40][O:41][C:42]([NH:44][C@@H:45]([C:49]([CH3:53])([S:51][CH3:52])[CH3:50])[C:46](O)=[O:47])=[O:43].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:40][O:41][C:42](=[O:43])[NH:44][C@@H:45]([C:49]([CH3:50])([S:51][CH3:52])[CH3:53])[C:46](=[O:47])[NH:1][C@@H:2]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C@@H:3]([OH:32])[CH2:4][C@H:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1)[NH:19][C:20](=[O:21])[C@H:22]([C:23]([CH3:26])([CH3:25])[CH3:24])[NH:27][C:28](=[O:31])[O:29][CH3:30]
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반응물 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 16037867methyl (1S)-1-[({(1S,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateHCID 86598805(2R)-2-[(methoxycarbonyl)amino]-3-methyl-3-(methylsulfanyl)butanoic Acid

생성물 1

HCID 11343134
Methyl(1r,4s,5s,7s,10s)-4-benzyl-10-tert-butyl-5-hydroxy-1-[1-methyl-1-(methylsulfanyl)ethyl]-2,9,12-trioxo-7-[4-(2-pyridinyl)benzyl]-13-oxa-3,8,11-triazatetradec-1-ylcarbamate
수율 39.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
25 °C

실험 절차

A solution containing the product from Example 2C (0.10 g, 0.18 mmol) in THF (2 mL) was treated with the product from Example 30A (0.05 g, 0.226 mmol), DEPBT (0.085 g, 0.28 mmol), and N,N-diisopropylethylamine (0.165 mL, 0.947 mmol), stirred at 25° C. for 1 hour, and partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane to give the title compound (0.052 g, 38% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 1.10 (s, 3 H), 1.21 (s, 3 H), 1.54 (m, 2 H), 1.98 (s, 3 H), 2.57 (m, 1 H), 2.75 (m, 3 H), 3.49 (s, 3 H), 3.56 (s, 3 H), 3.64 (m, 1 H), 3.82 (d, J=9.56 Hz, 1 H), 4.17 (m, 3 H), 4.83 (d, J=5.88 Hz, 1 H), 6.61 (d, J=9.56 Hz, 1 H), 6.90 (d, J=9.56 Hz, 1 H), 7.15 (m, 7 H), 7.31 (m, 1 H), 7.84 (m, 6 H), 8.63 (d, J=4.78 Hz, 1 H).

후처리

  1. custompartitioned between ethyl acetate and 10% Na2CO3 solution
  2. washThe organic phase was washed with additional 10% Na2CO3 solution and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane

출처 및 근거

ORD 기록
ord-76a9f557acab427aa7ff5ed38aaf513b
출처 데이터셋
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07834043B2

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