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

HRID 1174243
Notes
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Reaction equation

HRID 1174243 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][C:41]([CH3:61])([CH3:60])[C@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[CH3:58])[C:47]1=[O:59])[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]([CH3:61])([CH3:60])[C@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[CH3:58])[C:47]1=[O:59])[C:43]([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]([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)=[O:44]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

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 42626321(2S)-3,3-dimethyl-2-[3-(2-methylbenzyl)-2-oxo-1-imidazolidinyl]butanoic acid

Product 1

HCID 49763680
methyl (1S)-1-[({(1R,3S,4S)-4-({(2S)-3,3-dimethyl-2-[3-(2-methylbenzyl)-2-oxo-1-imidazolidinyl]butanoyl}amino)-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate
Yield 42%

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 65A (0.023 g, 0.076 mmol), DEPBT (0.017 g, 0.057 mmol), and N,N-diisopropylethylamine (0.033 mL, 0.189 mmol) and the mixture was stirred at 25° C. for 2 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 product was purified by reversed phase chromatography on a C18 column eluting with 5-100% acetonitrile in water (0.1% TFA). The product was partitioned between ethyl acetate and saturated NaHCO3 solution. The organic phase was washed brine, dried over MgSO4, filtered and concentrated to give the title compound (0.013 g, 42% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 0.89 (m, 9 H), 1.46 (m, 2 H), 2.29 (s, 3 H), 2.38 (m, 1 H), 2.76 (m, 5 H), 3.22 (m, 2 H), 3.53 (m, 4 H), 3.84 (d, J=9.93 Hz, 1 H), 3.95 (m, 1 H), 4.02 (s, 1 H), 4.18 (m, 2 H), 4.41 (m, 2 H), 6.88 (d, J=9.56 Hz, 1 H), 7.04 (m, 5 H), 7.21 (m, 6 H), 7.32 (m, 1 H), 7.53 (d, J=9.56 Hz, 1 H), 7.89 (m, 5 H), 8.65 (d, J=4.04 Hz, 1 H).

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 product was purified by reversed phase chromatography on a C18 column
  7. washeluting with 5-100% acetonitrile in water (0.1% TFA)
  8. customThe product was partitioned between ethyl acetate and saturated NaHCO3 solution
  9. washThe organic phase was washed brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-6028f6d8d8e04a4a8766e693d96af0b4
Source dataset
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07834043B2

Reaction notes

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