Trifluoroacetic acid → HCID 11445790, compound

HRID 1174271Notes

Reaction equation

HRID 1174271 reaction equation
[CH2:1]([C@H:8]([NH:48]C(=O)OC(C)(C)C)[C@@H:9]([OH:47])[CH2:10][C@H:11]([NH:25][C:26](=[O:46])[C@@H:27]([N:32]1[CH2:36][CH2:35][N:34]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([CH3:44])[N:39]=2)[C:33]1=[O:45])[C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[CH3:63][O:64][C:65]([NH:67][C@@H:68]([C:72]([CH3:75])([CH3:74])[CH3:73])[C:69]([OH:71])=O)=[O:66].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>ClCCl.C1COCC1>[CH2:1]([C@H:8]([NH:48][C:69]([C@@H:68]([NH:67][C:65](=[O:66])[O:64][CH3:63])[C:72]([CH3:75])([CH3:74])[CH3:73])=[O:71])[C@@H:9]([OH:47])[CH2:10][C@H:11]([NH:25][C:26](=[O:46])[C@@H:27]([N:32]1[CH2:36][CH2:35][N:34]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([CH3:44])[N:39]=2)[C:33]1=[O:45])[C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:17][CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 91210835HCID 91210835, compound

Product 1

HCID 11445790HCID 11445790, compoundYield 50.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 94A (0.042 g, 0.056 mmol) in dichloromethane (0.3 mL) was treated with trifluoroacetic acid (0.3 mL) and the mixture was stirred at 25° C. for 1 hour. The solvent was concentrated and the residue was dissolved in toluene and concentrated several times. A solution of the residue (0.056 mmol) in THF (0.6 mL) was treated with the product from Example 1F (0.011 g, 0.058 mmol), DEPBT (0.025 g, 0.083 mmol), and N,N-diisopropylethylamine (0.049 mL, 0.281 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 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, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated to give the title compound (0.023 g, 48% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.77(s, 9H), 0.81(s, 9H), 1.41-1.31(m, 1H), 1.59-1.49(m, 1H), 2.43(s, 3H), 2.70-2.59(m, 3H), 2.88-2.77(m, 1H), 3.25-3.12(m, 2H), 3.53(s, 3H), 3.64-3.44(m, 2H), 3.94-3.84(m, 2H), 4.08(s, 1H), 4.19-4.10(m, 2H), 4.43-4.26(m, 2H), 6.77-6.73(d, J=9.56 Hz, 1H), 7.03-7.01(d, J=7.72 Hz, 1H), 7.18-7.09(m, 5H), 7.28-7.25(d, J=8.46 Hz, 2H), 7.34-7.30(m, 2H), 7.53-7.50(d, J=9.93 Hz, 1H), 7.65-7.60(t, J=7.72 Hz, 1H), 7.92-7.83(m, 2H), 7.97-7.95(d, J=8.09 Hz, 2H), 8.17-8.15(d, J=8.46 Hz, 1H), 8.65-8.64(d, J=4.78 Hz, 1H).

Workup

  1. concentrationThe solvent was concentrated
  2. dissolutionthe residue was dissolved in toluene
  3. concentrationconcentrated several times
  4. stirringstirred at 25° C. for 2 hours
  5. custompartitioned between ethyl acetate and 10% Na2CO3 solution
  6. washThe organic phase was washed with additional 10% Na2CO3 solution and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by reversed phase chromatography on a C18 column
  11. washeluting with 5-100% acetonitrile in water (0.1% TFA)
  12. customThe product was partitioned between ethyl acetate and saturated NaHCO3
  13. washthe organic phase was washed with brine
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-83f3837c48164a84a25c853cda52c878
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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