4-Methylmorpholine → methyl (1S)-1-({[(1S,3S,4S)-1-benzyl-3-hydroxy-4-({(2S)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanoyl}amino)-5-phenylpentyl]amino}carbonyl)-2-methylbutylcarbamate

HRID 1174126ノート

反応式

HRID 1174126 の反応式
[NH2:1][C@@H:2]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:3]([OH:26])[CH2:4][C@@H:5]([NH:13][C:14]([C@@H:16]([NH:21][C:22](=[O:25])[O:23][CH3:24])[C@@H:17]([CH3:20])[CH2:18][CH3:19])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.FC(F)(F)C(O)=O.[CH3:41][C@@H:42]([CH2:64][CH3:65])[C@H:43]([N:47]1[CH2:51][CH2:50][N:49]([CH2:52][C:53]2[C:62]3[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=3)[N:56]=[CH:55][CH:54]=2)[C:48]1=[O:63])[C:44](O)=[O:45].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[CH2:6]([C@H:5]([NH:13][C:14]([C@@H:16]([NH:21][C:22](=[O:25])[O:23][CH3:24])[CH:17]([CH3:20])[CH2:18][CH3:19])=[O:15])[CH2:4][C@H:3]([OH:26])[C@@H:2]([NH:1][C:44](=[O:45])[C@@H:43]([N:47]1[CH2:51][CH2:50][N:49]([CH2:52][C:53]2[C:62]3[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=3)[N:56]=[CH:55][CH:54]=2)[C:48]1=[O:63])[CH:42]([CH3:41])[CH2:64][CH3:65])[CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67408554(2S,3S)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanoic acid trifluoroacetatHCID 86726166methyl (1S,2S)-1-({[(1S,3S,4S)-4-amino-1-benzyl-3-hydroxy-5-phenylpentyl]amino}carbonyl)-2-methylbutylcarbamate

生成物 1

HCID 86726168methyl (1S)-1-({[(1S,3S,4S)-1-benzyl-3-hydroxy-4-({(2S)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanoyl}amino)-5-phenylpentyl]amino}carbonyl)-2-methylbutylcarbamate収率 23%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

A solution containing the product from Example 5C (0.078 g, 0.171 mmol) in DMF (0.5 mL) was treated with the product from Example 4A (0.070 g, 0.205 mmol), EDAC (0.050 g, 0.261 mmol), HOBT (0.035 g, 0.259 mmol), and NMM (0.060 mL, 0.546 mmol) at 0° C., stirred at 25° C. for 16 hours, and partitioned between ethyl acetate and water. The organic phase was washed with 10% citric acid, diluted sodium bicarbonate, and brine, dried over MgSO4, filtered and concentrated. The residue was purified by reversed phase chromatography on a C18 column eluting with 5-100% acetonitrile in water (0.1% TFA) to give the title compound (0.030 g, 23% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.76 (m, 12 H), 1.00 (m, 2 H), 1.29 (m, 2 H), 1.49 (m, 3 H), 1.81 (m, 1 H), 2.65 (m, 5 H), 3.01 (m, 3 H), 3.54 (s, 3 H), 3.61 (m, 1 H), 3.75 (t, J=8.82 Hz, 1 H), 3.99 (d, J=11.03 Hz, 1 H), 4.13 (m, 2 H), 4.62 (d, J=7.35 Hz, 1 H), 4.80 (m, 2 H), 6.89 (d, J=9.56 Hz, 1 H), 6.98 (m, 5 H), 7.15 (m, 5 H), 7.32 (d, J=9.93 Hz, 1 H), 7.41 (d, J=4.41 Hz, 1 H), 7.66 (m, 2 H), 7.77 (t, J=6.99 Hz, 1 H), 8.06 (d, J=7.72 Hz, 1 H), 8.30 (d, J=8.09 Hz, 1 H), 8.88 (d, J=4.41 Hz, 1 H).

後処理

  1. custompartitioned between ethyl acetate and water
  2. washThe organic phase was washed with 10% citric acid, diluted sodium bicarbonate, and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reversed phase chromatography on a C18 column
  7. washeluting with 5-100% acetonitrile in water (0.1% TFA)

出典と根拠

ORDレコード
ord-b07420bfee9d49eebafe1bd5f45604a4
出典データセット
uspto-grants-2010_11
特許番号
US07834043B2

反応ノート

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