Diisopropylethylamine → HCID 11181961, compound

HRID 1174292Notes

Reaction equation

HRID 1174292 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@@H:41]([CH2:58][CH3:59])[C@H:42]([NH:46][C:47]([N:49]([CH3:57])[CH2:50][C:51]1[N:52]=[C:53]([CH3:56])[S:54][CH:55]=1)=[O:48])[C:43](O)=[O:44].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:43](=[O:44])[C@H:42]([CH:41]([CH2:58][CH3:59])[CH3:40])[NH:46][C:47](=[O:48])[N:49]([CH3:57])[CH2:50][C:51]1[N:52]=[C:53]([CH3:56])[S:54][CH:55]=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 61818371HCID 61818371, compound

Product 1

HCID 11181961HCID 11181961, compoundYield 78.4%

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 109E (0.018 g, 0.061 mmol), DEPBT (0.021 g, 0.071 mmol), and N,N-diisopropylethylamine (0.041 mL, 0.235 mmol), stirred at 25° C. for 2 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 0-100% ethyl acetate/dichloromethane, followed by 0-10% methanol in ethyl acetate, to give the title compound (0.030 g, 78% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.78 (m, 16 H), 1.01 (m, 1 H), 1.36 (m, 1 H), 1.50 (m, 2 H), 1.70 (m, 1 H), 2.61 (s, 3 H), 2.73 (m, 3 H), 2.86 (s, 3 H), 3.49 (s, 3 H), 3.62 (m, 1 H), 3.83 (d, J=9.93 Hz, 1 H), 3.98 (t, J=7.91 Hz, 1 H), 4.11 (m, 2 H), 4.43 (m, 2 H), 4.86 (d, J=5.88 Hz, 1 H), 6.19 (d, J=8.09 Hz, 1 H), 6.62 (d, J=9.56 Hz, 1 H), 7.16 (m, 8 H), 7.31 (m, 1 H), 7.42 (d, J=9.19 Hz, 1 H), 7.77 (d, J=8.09 Hz, 1 H), 7.85 (m, 4 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 chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-2c6e9592d3494125b35726443998535b
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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