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

HRID 1174123Notes

Reaction equation

HRID 1174123 reaction equation
[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:17]([CH3:20])([CH3:19])[CH3:18])=[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])[C:17]([CH3:20])([CH3:19])[CH3:18])=[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

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 17756282methyl (1S)-1-({[(1S,3S,4S)-4-amino-1-benzyl-3-hydroxy-5-phenylpentyl]amino}carbonyl)-2,2-dimethylpropylcarbamateHCID 67408554(2S,3S)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanoic acid trifluoroacetat

Product 1

HCID 11308774methyl (1S)-1-({[(1S,3S,4S)-1-benzyl-3-hydroxy-4-({(2S)-3-methyl-2-[2-oxo-3-(4-quino linylmethyl)-1-imidazolidinyl]pentanoyl}amino)-5-phenylpentyl]amino}carbonyl)-2,2-dimethylpropylcarbamateYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 3D (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 0.79 (m, 15 H), 1.00 (m, 1 H), 1.25 (m, 1 H), 1.51 (m, 2 H), 1.82 (m, 1 H), 2.64 (m, 5 H), 3.02 (m, 3 H), 3.55 (s, 3 H), 3.63 (m, 1 H), 3.82 (d, J=9.93 Hz, 1 H), 3.99 (d, J=11.03 Hz, 1 H), 4.13 (m, 2 H), 4.64 (d, J=7.72 Hz, 1 H), 4.80 (m, 2 H), 6.62 (d, J=9.93 Hz, 1 H), 6.98 (m, 5 H), 7.14 (m, 5 H), 7.32 (d, J=9.56 Hz, 1 H), 7.41 (d, J=4.41 Hz, 1 H), 7.62 (t, J=7.54 Hz, 1 H), 7.76 (m, 2 H), 8.06 (d, J=7.72 Hz, 1 H), 8.30 (d, J=8.46 Hz, 1 H), 8.88 (d, J=4.41 Hz, 1 H).

Workup

  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)

Sources & evidence

ORD record
ord-67112b75535445968c4b1338a64912cb
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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