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

HRID 1174140Notes

Reaction equation

HRID 1174140 reaction equation
[NH2:1][C@@H:2]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:3][C@H:4]([OH:26])[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.[CH3:34][C@@H:35]([CH2:54][CH3:55])[C@H:36]([N:40]1[CH2:44][CH2:43][N:42]([CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([CH3:52])[N:47]=2)[C:41]1=[O:53])[C:37](O)=[O:38].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[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])[C@@H:4]([OH:26])[CH2:3][C@@H:2]([NH:1][C:37](=[O:38])[C@@H:36]([N:40]1[CH2:44][CH2:43][N:42]([CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([CH3:52])[N:47]=2)[C:41]1=[O:53])[CH:35]([CH3:34])[CH2:54][CH3:55])[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

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 66891343(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoic AcidHCID 86726173methyl (1S,2S)-1-({[(1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl]amino}carbonyl)-2-methylbutylcarbamate

Product 1

HCID 86726175methyl (1S)-1-[({(1S,2S,4S)-1-benzyl-2-hydroxy-4-[((2S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoyl)amino]-5-phenylpentyl}amino)carbonyl]-2-methylbutylcarbamateYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 9B (0.36 g, 0.79 mmol) in THF (8 mL) was treated with the product from Example 7B (0.33 g, 0.79 mmol), DEPBT (0.355 g, 1.19 mmol), and N,N-diisopropylethylamine (0.70 mL, 4.02 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 0-50% acetone/dichloromethane to give the title compound (0.264 g, 45% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.75 (m, 12 H), 0.94 (m, 2 H), 1.29 (m, 2 H), 1.46 (m, 2 H), 1.62 (m, 1 H), 1.80 (m, 1 H), 2.43 (m, 4 H), 2.68 (m, 3 H), 2.88 (m, 1 H), 3.08 (m, 3 H), 3.56 (m, 4 H), 3.84 (m, 2 H), 4.15 (m, 2 H), 4.34 (s, 2 H), 4.84 (d, J=5.88 Hz, 1 H), 7.03 (m, 7 H), 7.15 (m, 6 H), 7.39 (d, J=9.19 Hz, 1 H), 7.66 (t, J=7.72 Hz, 1 H), 7.83 (d, J=8.82 Hz, 1 H).

Workup

  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 0-50% acetone/dichloromethane

Sources & evidence

ORD record
ord-70dc4f59ab6145d482bef6a1d45ba73d
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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