Diisopropylethylamine → Methyl(1s,4r,6s,7s,10s)-7-benzyl-1,10-ditert-butyl-6-hydroxy-2,9,12-trioxo-4-[4-(2-pyridinyl)benzyl]-13-oxa-3,8,11-triazatetradec-1-ylcarbamate

HRID 1174107Notes

Reaction equation

HRID 1174107 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]([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][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>C1COCC1>[CH3:30][O:29][C:28](=[O:31])[NH:27][C@@H:22]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:20](=[O:21])[NH:19][C@H:5]([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)[CH2:4][C@H:3]([OH:32])[C@H:2]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[NH:1][C:46](=[O:47])[C@H:45]([C:49]([CH3:51])([CH3:50])[CH3:52])[NH:44][C:42](=[O:43])[O:41][CH3:40]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 42625467methyl (1S)-1-[({(1R,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate

Product 1

HCID 11763944Methyl(1s,4r,6s,7s,10s)-7-benzyl-1,10-ditert-butyl-6-hydroxy-2,9,12-trioxo-4-[4-(2-pyridinyl)benzyl]-13-oxa-3,8,11-triazatetradec-1-ylcarbamateYield 81.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of the product of Example 1H (0.18 g, 0.33 mmol) in THF (3.3 mL) was treated with the product of Example 1F (0.11 g, 0.60 mmol), DEPBT (0.15 g, 0.50 mmol), and N,N-diisopropylethylamine (0.29 mL, 1.66 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%-75% ethyl acetate in chloroform to give the title product (0.19 g, 81% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.75 (s, 9 H), 0.78 (s, 9 H), 1.28 (m, 2 H), 1.55 (m, 1 H), 2.70 (m, 4 H), 3.55 (d, J=11.77 Hz, 6 H), 3.85 (m, 3 H), 4.15 (m, 1 H), 4.80 (d, J=5.15 Hz, 1 H), 6.75 (d, J=9.19 Hz, 1 H), 6.86 (d, J=9.56 Hz, 1 H), 7.13 (m, 5 H), 7.22 (d, J=8.46 Hz, 2 H), 7.32 (m, 1 H), 7.52 (d, *8.82 Hz, 1 H), 7.88 (m, 5 H), 8.64 (d, j=4.41 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%-75% ethyl acetate in chloroform

Sources & evidence

ORD record
ord-e59c6adec83b40e4ba906ba7496c1ee7
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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