Diisopropylethylamine → HCID 86726239, compound

HRID 1174340Notes

Reaction equation

HRID 1174340 reaction equation
[NH2:1][C@@H:2]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:3][C@H:4]([OH:41])[C@@H:5]([NH:19][C:20](=[O:40])[C@@H:21]([N:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[N:33]=2)[C:27]1=[O:39])[C:22]([CH3:25])([CH3:24])[CH3:23])[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.[CH3:49][O:50][C:51]([NH:53][C@@H:54]([C:58]([CH3:61])([CH3:60])[CH3:59])[C:55](O)=[O:56])=[O:52].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:42]([C@H:2]([NH:1][C:55]([C@@H:54]([NH:53][C:51](=[O:52])[O:50][CH3:49])[C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:3][C@H:4]([OH:41])[C@@H:5]([NH:19][C:20](=[O:40])[C@@H:21]([N:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[N:33]=2)[C:27]1=[O:39])[C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:11][CH:12]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 67406613HCID 67406613, compound

Product 1

HCID 86726239HCID 86726239, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 132B (0.023 mmol) in THF (0.25 mL) were added the product from Example 1F (0.005 g, 0.026 mmol), DEPBT (0.010 g, 0.033 mmol), and N,N-diisopropylethylamine (0.020 mL, 0.115 mmol), stirred at 25° C. for 16 hours, and partitioned between chloroform and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and then brine, dried over MgSO4, filtered and concentrated. The product was purified by chromatography on silica gel eluting with 0-100% ethyl acetate/dichloromethane, followed by 0-5% methanol in ethyl acetate to give the product. The product was re-purified by preparative TLC eluting with 5% methanol in ethyl acetate to give the title compound (0.002 g, 11% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.82 (s, 9 H), 0.91 (s, 9 H), 1.25 (m, 1 H), 1.52 (m, 2 H), 2.41 (m, 1 H), 2.43 (s, 3 H), 2.74 (m, 3H), 2.97 (q, J=9.2 Hz, 1 H), 3.24 (m, 1 H), 3.54 (s, 3 H), 3.66 (m, 1 H), 3.82 (d, J=9.9 Hz, 2 H), 4.09 (s, 1 H), 4.17 (m, 1 H), 4.25 (d, J=16 Hz, 1 H), 4.35 (d, J=16 Hz, 1 H), 4.53 (d, J=7.4 Hz, 1 H), 6.63 (d, J=9.9 Hz, 1 H), 7.11 (m, 8 H), 7.21 (d, J=8.09 Hz, 2 H), 7.51 (d, J=8.56 Hz, 1 H), 7.62 (t, J=7.7 Hz, 1 H), 7.75 (m, 2H), 7.83 (d, J=8.09 Hz, 1 H), 8.60 (d, J=4.1 Hz, 1 H).

Workup

  1. custompartitioned between chloroform and 10% Na2CO3 solution
  2. washThe organic phase was washed with additional 10% Na2CO3 solution
  3. dry with materialbrine, dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by chromatography on silica gel eluting with 0-100% ethyl acetate/dichloromethane
  7. customto give the product
  8. customThe product was re-purified by preparative TLC
  9. washeluting with 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-0ab549455a4543df87b1e917e7c347b2
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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