Trifluoroacetic acid → HCID 46893528, compound

HRID 1879628Notes

Reaction equation

HRID 1879628 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:31]2[N:32]([CH3:45])[N:33]=[C:34]3[C:39]=2[CH:38]=[C:37]([C:40]([F:43])([F:42])[F:41])[CH:36]=[C:35]3[Cl:44])[CH:9]([C:13]2[CH:30]=[CH:29][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:31]2[N:32]([CH3:45])[N:33]=[C:34]3[C:39]=2[CH:38]=[C:37]([C:40]([F:41])([F:42])[F:43])[CH:36]=[C:35]3[Cl:44])[CH:9]([C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[O:18])=[CH:29][CH:30]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67490685HCID 67490685, compound

Product 1

HCID 46893528HCID 46893528, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the faster-eluting enantiomer of the product from Step B (4 mg, 0.006 mmol) in DCM (1 mL) was added TFA (1 mL, 13 mmol), and the solution was stirred for 30 minutes at RT. The solution was concentrated, then the residue was purified by reverse phase HPLC eluting with acetonitrile/water+0.1% TFA. Following lyophilization, this afforded the enantiopure title compound as a white solid. This was the most potent glucagon receptor antagonist of the four stereoisomeric compounds. 1H NMR (600 MHz, CD3OD): δ 8.44 (s, 1 H); 7.60 (d, J=8.3 Hz, 2H); 7.52 (d, J=8.0 Hz, 2H); 7.40 (d, J=8.3 Hz, 2H); 7.39 (s, 1H); 7.32 (d, J=8.0 Hz, 2H); 5.02 (d, J=11.9 Hz, 1H); 4.07 (s, 3H); 4.02 (td, J=11.3, 3.4 Hz, 1H); 3.51 (t, J=7.0 Hz, 2H); 2.54 (t, J=7.0 Hz, 2H); 1.76-1.61 (m, 2H); 1.19-1.02 (m, 2H); 0.78 (t, J=7.3 Hz, 3H); LC1 2.44 min. (M+H)− 606.

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was purified by reverse phase HPLC
  3. washeluting with acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-d25caa915826417eb06d6e1abe5d137d
Source dataset
uspto-grants-2012_11
Patent number
US08318667B2

Reaction notes

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