Trifluoroacetic acid → HCID 91566627, compound

HRID 1174173Notes

Reaction equation

HRID 1174173 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 90702565HCID 90702565, compound

Product 1

HCID 91566627HCID 91566627, compoundYield 40.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 24A (0.129 g, 0.17 mmol) in dichloromethane (0.8 mL) was treated with trifluoroacetic acid (0.8 mL), stirred at 25° C. for 1 hour and concentrated. A solution of the residue (0.17 mmol) in THF (1.8 mL) was treated with the product from Example 1F (0.033g, 0.17 mmol), DEPBT (0.077 g, 0.26 mmol), and N,N-diisopropylethylamine (0.30 mL, 1.72 mmol), stirred at 25° C. for 18 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 0-5% methanol/ethyl acetate to give the title compound (0.057 g, 40% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.85 (d, J=1.10 Hz, 18 H), 1.55 (m, 2 H), 2.43 (m, 5 H), 2.72 (m, 4 H), 2.95 (m, 1 H), 3.19(m, 1 H), 3.58 (m, 4 H), 3.93 (d, J=9.56 Hz, 1 H), 3.99 (s, 1 H), 4.28 (m, 4 H), 4.84 (d, J=5.52 Hz, 1 H), 6.82 (d, J=9.93 Hz, 1 H), 6.97 (d, J=7.72 Hz, 1 H), 7.16 (m, 8 H), 7.29 (m, 1 H), 7.52 (d, J=8.82 Hz, 1 H), 7.61 (t, J=7.72 Hz, 1 H), 7.79 (m, 4 H), 7.95 (d, J=8.82 Hz, 1 H), 8.61 (d, J=4.78 Hz, 1 H).

Workup

  1. concentrationconcentrated
  2. stirringstirred at 25° C. for 18 hours
  3. custompartitioned between ethyl acetate and 10% Na2CO3 solution
  4. washThe organic phase was washed with additional 10% Na2CO3 solution and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel eluting with 0-5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-fa3c1652b7004775ad537762418113c2
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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