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Diisopropylethylamine → methyl (1S)-1-[({(1S,2S,4S)-2-hydroxy-4-[((2S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoyl)amino]-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate

HRID 1174175
ノート
印刷プレビュー

反応式

HRID 1174175 の反応式
[NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:3][C@H:4]([OH:32])[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][C@@H:41]([CH2:60][CH3:61])[C@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([CH3:58])[N:53]=2)[C:47]1=[O:59])[C:43](O)=[O:44].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[OH:32][C@@H:4]([CH2:3][C@@H:2]([NH:1][C:43](=[O:44])[C@@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([CH3:58])[N:53]=2)[C:47]1=[O:59])[CH:41]([CH3:40])[CH2:60][CH3:61])[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C@@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:25])([CH3:26])[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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 42625793methyl (1S)-1-[({(1S,2S,4S)-4-amino-2-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateHCID 66891343(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoic Acid

生成物 1

HCID 86726182
methyl (1S)-1-[({(1S,2S,4S)-2-hydroxy-4-[((2S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoyl)amino]-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate
収率 54.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
25 °C

実験手順

A solution containing the product from Example 23S (0.025 g, 0.047 mmol) in THF (0.5 mL) was treated with the product from Example 7B (0.025 g, 0.060 mmol), DEPBT (0.025 g, 0.084 mmol), and N,N-diisopropylethylamine (0.040 mL, 0.230 mmol), stirred at 25° C. for 2 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 eluting with 0-10% methanol in ethyl acetate to give the title compound (0.021 g, 54% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.60 (d, J=6.62 Hz, 3 H), 0.73 (t, J=7.17 Hz, 3 H), 0.87(m, 10 H), 1.27 (m, 1 H), 1.54 (m, 2 H), 1.75 (m, 1 H), 2.43 (m, 4 H), 2.66 (m, 1 H), 2.77 (d, J=6.99 Hz, 2 H), 2.91 (m, 1 H), 3.12 (m, 3 H), 3.51 (s, 3 H), 3.59 (m, 1 H), 3.85 (d, J=11.03 Hz, 1 H), 3.94 (d, J=9.56 Hz, 1 H), 4.14 (m, 2 H), 4.33 (s, 2 H), 4.81 (d, J=5.15 Hz, 1 H), 6.80 (d, J=9.56 Hz, 1 H), 7.07 (m, 7 H), 7.30 (d, J=7.72 Hz, 3 H), 7.58 (d, J=8.82 Hz, 1 H), 7.65 (t, J=7.54 Hz, 1 H), 7.87 (m, 5 H), 8.63 (d, J=4.04 Hz, 1 H).

後処理

  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. washby eluting with 0-10% methanol in ethyl acetate

出典と根拠

ORDレコード
ord-265e04fd92964c93b82aa51c6c85c405
出典データセット
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07834043B2

反応ノート

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