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

HRID 1174201Notes

Reaction equation

HRID 1174201 reaction equation
[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:41]([CH3:62])([CH3:61])[C@H:42]([N:46]1[CH2:50][C:49](=[O:51])[N:48]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[N:54]=2)[C:47]1=[O:60])[C:43](O)=[O:44].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:40][C:41]([CH3:62])([CH3:61])[C@H:42]([N:46]1[CH2:50][C:49](=[O:51])[N:48]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[N:54]=2)[C:47]1=[O:60])[C:43]([NH:1][C@@H:2]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=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]([CH3:25])([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)=[O:44]

Participants

6

Reactant 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 67407844(2S)-3,3-dimethyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanoic Acid

Product 1

HCID 86726185methyl (1S)-1-[({(1S,2S,4S)-4-[((2S)-3,3-dimethyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanoyl)amino]-2-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 23S (0.020 g, 0.038 mmol) in THF (0.4 mL) was treated with the product from Example 46E (0.020 g, 0.046 mmol), DEPBT (0.017 g, 0.057 mmol), and N,N-diisopropylethylamine (0.035 mL, 0.201 mmol), stirred at 25° C. for 1 hour, 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 to give the title compound (0.021 g, 67% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 0.88 (s, 9 H), 1.55 (m, 2 H), 2.29 (m, 1 H), 2.39 (s, 3H), 2.75 (m, 3 H), 3.15 (d, J=18.38 Hz, 1 H), 3.52 (s, 3 H), 3.61 (m, 1 H), 3.94 (m, 2 H), 4.19 (m, 3 H), 4.68 (d, J=10.30 Hz, 2 H), 4.89 (d, J=5.52 Hz, 1 H), 6.83 (d, J=9.93 Hz, 1 H), 7.00 (m, 6 H), 7.13 (d, J=7.72 Hz, 1 H), 7.31 (m, 3 H), 7.64 (m, 2 H), 7.88 (m, 4 H), 8.09 (d, J=9.19 Hz, 1 H), 8.63 (d, J=4.78 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 0-100% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-aff4efc3e22946b3ae22b48a4d9f8b5b
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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