Diisopropylethylamine → methyl (1S)-1-[({(1R,3S,4S)-4-{[(2S)-2-(3-benzyl-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoyl]amino}-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate

HRID 1174234노트

반응식

HRID 1174234 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.[CH2:40]([N:47]1[CH2:51][CH2:50][N:49]([C@@H:52]([C:56]([CH3:59])([CH3:58])[CH3:57])[C:53](O)=[O:54])[C:48]1=[O:60])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:40]([N:47]1[CH2:51][CH2:50][N:49]([C@@H:52]([C:56]([CH3:58])([CH3:57])[CH3:59])[C:53]([NH:1][C@@H:2]([CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[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]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[CH:9][CH:8]=2)=[O:54])[C:48]1=[O:60])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 42625467methyl (1S)-1-[({(1R,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateHCID 42626247(2S)-2-(3-benzyl-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoic acid

생성물 1

HCID 42625714methyl (1S)-1-[({(1R,3S,4S)-4-{[(2S)-2-(3-benzyl-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoyl]amino}-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate수율 74.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
25 °C

실험 절차

A solution containing the product from Example 1H (0.040 g, 0.075 mmol) in THF (0.6 mL) was treated with the product from Example 70A (0.027 g, 0.092 mmol), DEPBT (0.034 g, 0.114 mmol), and N,N-diisopropylethylamine (0.066 mL, 0.379 mmol), stirred at 25° C. for 16 hours, 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, followed by elution with 0-5% methanol in ethyl acetate to give the title compound (0.045 g, 73% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 0.87 (s, 9 H), 1.38 (t, J=11.58 Hz, 1 H), 1.54 (m, 1 H), 2.41 (m, 1 H), 2.64 (m, 3 H), 2.87 (m, 3 H), 3.19 (m, 1 H), 3.53 (m, 4 H), 3.84 (d, J=9.56 Hz, 1 H), 3.95 (m, 1 H), 4.04 (s, 1 H), 4.18 (m, 1 H), 4.29 (m, 2 H), 4.45 (d, J=7.35 Hz, 1 H), 6.88 (d, J=9.56 Hz, 1 H), 7.05 (m, 5 H), 7.30 (m, 8 H), 7.53 (d, J=9.56 Hz, 1 H), 7.90 (m, 5 H), 8.65 (d, J=4.41 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
  7. washfollowed by elution with 0-5% methanol in ethyl acetate

출처 및 근거

ORD 기록
ord-a3d80b6d49804de0b3acf2db5b66561a
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834043B2

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