Diisopropylethylamine → Methyl(1s,4s,5s,7s,10s)-4-benzyl-1,10-di-tert-butyl-5-hydroxy-2,9,12-trioxo-7-(4-pyridin-3-ylbenzyl)-13-oxa-3,8,11-triazatetradec-1-ylcarbamate

HRID 1174368Notes

Reaction equation

HRID 1174368 reaction equation
[NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@@H:3]([OH:32])[CH2:4][C@@H:5]([NH:19][C:20](=[O:31])[C@H:21]([C:27]([CH3:30])([CH3:29])[CH3:28])[NH:22][C:23]([O:25][CH3:26])=[O:24])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:9][CH:8]=1.[CH3:40][O:41][C:42]([NH:44][C@@H:45]([C:49]([CH3:52])([CH3:51])[CH3:50])[C:46](O)=[O:47])=[O:43].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>O1CCCC1>[CH3:40][O:41][C:42](=[O:43])[NH:44][C@@H:45]([C:49]([CH3:51])([CH3:50])[CH3:52])[C:46](=[O:47])[NH:1][C@@H:2]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C@@H:3]([OH:32])[CH2:4][C@H:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:9][CH:8]=1)[NH:19][C:20](=[O:31])[C@H:21]([C:27]([CH3:30])([CH3:29])[CH3:28])[NH:22][C:23](=[O:24])[O:25][CH3:26]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 67407163HCID 67407163, compound

Product 1

HCID 76900768Methyl(1s,4s,5s,7s,10s)-4-benzyl-1,10-di-tert-butyl-5-hydroxy-2,9,12-trioxo-7-(4-pyridin-3-ylbenzyl)-13-oxa-3,8,11-triazatetradec-1-ylcarbamateYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution containing the product from Example 148E (0.17 mmol) in tetrahydrofuran (1.7 mL) were added the product from Example 1F (0.036 g, 0.190 mmol), DEPBT (0.077 g, 0.258 mmol), and N,N-diisopropylethylamine (0.15 mL, 0.861 mmol) and the mixture was stirred at room temperature for 18 hours. The mixture was partitioned between ethyl acetate and 10% Na2CO3 solution. The organic was washed with additional 10% Na2CO3 solution and then brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on reverse phase HPLC on C18 column eluting with a gradient starting with water and ending with methanol to give the product (0.044 g, 37% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 0.82 (s, 9 H), 1.42-1.59 (m, 2 H), 2.67-2.79 (m, 3 H), 3.47 (s, 3 H), 3.59-3.67 (m, 1 H), 3.81 (d, J=9.6 Hz, 1 H), 3.91 (d, J=9.6 Hz, 1 H), 4.02-4.21 (m, 2 H), 4.87 (d, J=5.2 Hz, 1 H), 6.65 (d, J=9.6 Hz, 1 H), 6.80 (d, J=9.9 Hz, 1 H), 7.12-7.23 (m, 8 H), 7.45-7.55 (m, 4 H), 7.80 (d, J=8.5 Hz, 1 H), 8.01 (d, J=8.1 Hz, 1 H), 8.54 (d, J=4.8 Hz, 1 H), 8.83 (d, J=1.8 Hz, 1 H).

Workup

  1. customThe mixture was partitioned between ethyl acetate and 10% Na2CO3 solution
  2. washThe organic was washed with additional 10% Na2CO3 solution
  3. dry with materialbrine, dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was chromatographed on reverse phase HPLC on C18 column
  7. washeluting with a gradient

Sources & evidence

ORD record
ord-2f736eebbfca4731b4422389c1730315
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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