Diisopropylethylamine → HCID 11239931, compound

HRID 1174210Notes

Reaction equation

HRID 1174210 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.[CH:40]([C:43]1[S:44][CH:45]=[C:46]([CH2:48][N:49]2[C:53](=[O:54])[CH2:52][N:51]([C@@H:55]([C@@H:59]([CH3:62])[CH2:60][CH3:61])[C:56](O)=[O:57])[C:50]2=[O:63])[N:47]=1)([CH3:42])[CH3:41].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:56](=[O:57])[C@@H:55]([N:51]1[CH2:52][C:53](=[O:54])[N:49]([CH2:48][C:46]2[N:47]=[C:43]([CH:40]([CH3:42])[CH3:41])[S:44][CH:45]=2)[C:50]1=[O:63])[CH:59]([CH3:62])[CH2:60][CH3:61])[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 67406416HCID 67406416, compound

Product 1

HCID 11239931HCID 11239931, compoundYield 67.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 2C (0.030 g, 0.056 mmol) in THF (0.5 mL) was treated with the product from Example 56E (0.026 g, 0.073 mmol), DEPBT (0.025 g, 0.085 mmol), and N,N-diisopropylethylamine (0.049 mL, 0.282 mmol), stirred at 25° C. for 1 hour, 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 elution with 0-5% methanol in ethyl acetate to give the title compound (0.033 g, 67% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.66 (d, J=6.62 Hz, 3 H), 0.73 (t, J=7.35 Hz, 3 H), 0.88 (m, 12 H), 1.26 (s, 3 H), 1.29 (s, 3 H), 1.50 (m, 2 H), 1.73 (m, 1 H), 2.69 (m, 4 H), 3.10 (d, J=18.38 Hz, 1 H), 3.50 (s, 3 H), 3.78 (m, 3 H) 4.17 (m, 3 H), 4.66 (m, 3 H), 6.67 (d, J=9.93 Hz, 1 H), 6.99 (m, 3 H), 7.07 (m, 2 H), 7.23 (m, 3 H), 7.31 (m, 1 H), 7.85 (m, 6 H), 8.63 (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 0-100% ethyl acetate/dichloromethane
  7. washfollowed by elution with 0-5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-b86865b7ea7c4401b55540a162c32b58
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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