Diisopropylethylamine → Methyl(1s,4r,6s,7s,10s)-7-benzyl-1,10-ditert-butyl-6-hydroxy-13-methyl-2,9,12-trioxo-14-phenyl-4-[4-(2-pyridinyl)benzyl]-3,8,11,13-tetraazatetradec-1-ylcarbamate

HRID 1174225Notes

Reaction equation

HRID 1174225 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.[CH2:40]([N:47]([CH3:59])[C:48]([NH:50][C@@H:51]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:52](O)=[O:53])=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.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:52](=[O:53])[C@H:51]([C:55]([CH3:57])([CH3:56])[CH3:58])[NH:50][C:48](=[O:49])[N:47]([CH3:59])[CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 42625467methyl (1S)-1-[({(1R,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateHCID 61186392(2S)-2-({[benzyl(methyl)amino]carbonyl}amino)-3,3-dimethylbutanoic Acid

Product 1

HCID 86726189Methyl(1s,4r,6s,7s,10s)-7-benzyl-1,10-ditert-butyl-6-hydroxy-13-methyl-2,9,12-trioxo-14-phenyl-4-[4-(2-pyridinyl)benzyl]-3,8,11,13-tetraazatetradec-1-ylcarbamateYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 1H (0.020 g, 0.038 mmol) in THF (0.4 mL) was treated with the product from Example 63C (0.013 g, 0.047 mmol), DEPBT (0.017 g, 0.057 mmol), and N,N-diisopropylethylamine (0.035 mL, 0.201 mmol) and the mixture was stirred at 25° C. for 16 hours. The mixture was 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 (0.022 g, 74% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.75(m, 9H), 0.78(m, 9H), 1.35-1.22(m, 1H), 1.65-1.54(m, 1H), 2.77-2.60(m, 4H), 2.79(s, 3H), 3.57(s, 3H), 3.83-3.77(m, 1H), 3.94-3.83(m, 1H), 4.09-4.06(d, J=8.82 Hz, 1H), 4.21-4.10(m, 1H), 4.51-4.38(m, 2H), 4.77-4.75(d, J=5.52 Hz, 1H), 5.43-5.40(d, J=8.82 Hz, 1H), 6.85-6.82(d, J=9.52 Hz, 1H), 7.26-7.10(m, 10H), 7.35-7.30(m, 1H). 3H), 7.60-7.57(d, J=9.19, 1H), 7.79-7.77(d, J=7.72 Hz, 1H), 7.93-7.82(m, 4H), 8.65-8.62(m, 1H).

Workup

  1. customThe mixture was partitioned 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-8ec3e83e1f4d4bdeb6aa923f49e0d3bd
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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