Diisopropylethylamine → HCID 42625641, compound

HRID 1174233Notes

Reaction equation

HRID 1174233 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]1[CH:43]=[C:44]([CH:60]=[CH:61][CH:62]=1)[CH2:45][N:46]1[CH2:50][CH2:49][N:48]([C@@H:51]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:52](O)=[O:53])[C:47]1=[O:59].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[OH:32][C@H:3]([C@@H:2]([NH:1][C:52](=[O:53])[C@@H:51]([N:48]1[CH2:49][CH2:50][N:46]([CH2:45][C:44]2[CH:60]=[CH:61][CH:62]=[C:42]([O:41][CH3:40])[CH:43]=2)[C:47]1=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[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

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 16037867methyl (1S)-1-[({(1S,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateHCID 42626319HCID 42626319, compound

Product 1

HCID 42625641HCID 42625641, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 2C (0.025 g, 0.047 mmol) in THF (0.5 mL) was treated with the product from Example 71A (0.020 g, 0.062 mmol), DEPBT (0.021 g, 0.071 mmol), and N,N-diisopropylethylamine (0.041 mL, 0.235 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 purified by reversed phase chromatography on a C18 column eluting with a gradient starting 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 (0.024 g, 59% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.83 (s, 9 H), 0.89 (s, 9 H), 1.55 (m, 2 H), 2.32 (m, 1 H), 2.80 (m, 6 H), 3.18 (m, 1 H), 3.50 (s, 3 H), 3.65 (m, 1 H), 3.74 (s, 3 H), 3.85 (d, J=9.93 Hz, 1 H), 4.20 (m, 5 H), 4.54 (d, J=7.72 Hz, 1 H), 6.63 (d, J=9.93 Hz, 1 H), 6.85 (m, 3 H), 7.08 (m, 5 H), 7.28 (m, 4 H), 7.48 (d, J=9.56 Hz, 1 H), 7.86 (m, 5 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 purified by reversed phase chromatography on a C18 column
  7. washeluting with a gradient
  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-f41e96da9a804401ad2c7f3a8e6795e0
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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