Trifluoroacetic acid → HCID 57919592, compound

HRID 1952475Notes

Reaction equation

HRID 1952475 reaction equation
[NH2:1][C:2]1[CH:37]=[CH:36][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:17]=[C:18]([CH:33]=[CH:34][CH:35]=4)[CH2:19][CH2:20][N:21]([CH2:29][CH2:30][O:31][CH3:32])C(=O)OC(C)(C)C)[S:15][C:8]=23)=[C:4]([F:38])[CH:3]=1.C(O)C.C1(C)C=CC=CC=1.[F:49][C:50]1[CH:55]=[CH:54][C:53]([CH2:56][C:57]([N:59]=[C:60]=[S:61])=[O:58])=[CH:52][CH:51]=1.FC(F)(F)C(O)=O>ClCCl>[F:38][C:4]1[CH:3]=[C:2]([NH:1][C:60]([NH:59][C:57](=[O:58])[CH2:56][C:53]2[CH:54]=[CH:55][C:50]([F:49])=[CH:51][CH:52]=2)=[S:61])[CH:37]=[CH:36][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:35]=[CH:34][CH:33]=[C:18]([CH2:19][CH2:20][NH:21][CH2:29][CH2:30][O:31][CH3:32])[CH:17]=3)[S:15][C:8]=12

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 21863594Toluene ethanol2×HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 57919557HCID 57919557, compound

Product 1

HCID 57919592HCID 57919592, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 156 (0.17 g, 0.32 mmol) in 1:1 absolute ethanol/toluene (20 mL), p-fluorophenylacetyl isothiocyanate (0.11 g, 0.56 mmol) in 1:1 absolute ethanol/toluene (5 mL) was added and the reaction was allowed to stir for 2 h at r.t. The solvents were removed under reduced pressure and the residue was purified by chromatography on silica gel (75% EtOAc/hexane) to give the intermediate Boc-protected product [not shown in the scheme] as a white solid. This material was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (3 mL) and stirred for 6 h at r.t. The mixture was then concentrated and the residue was purified by Gilson reverse phase HPLC (Aquasil C-18 column, 35-85% MeOH/H2O+HCO2H, 30 min. linear gradient elution) and lyophilized to afford title compound 157(0.100 g, 50% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.55 (d, J=5.3 Hz, 1H), 8.24 (s, 1H), 8.06 (s, 1H), 8.03-8.00 (m, 1H), 7.76 (s, 1H), 7.73 (d, J=7.8 Hz, 1H), 7.57-7.53 (m, 2H), 7.43 (t, J=7.6 Hz, 1H), 7.40-7.35 (m, 2H), 7.32 (d, J=7.6 Hz, 1H), 7.21-7.16 (m, 2H), 6.67 (d, J=5.5 Hz, 1H), 3.84 (s, 2H), 3.43 (t, J=5.5 Hz, 2H), 3.24 (s, 3H), 2.92-2.82 (m, 4H), 2.79 (t, J=5.5 Hz, 2H) (presumably as a formate salt). MS (m/z): 633.2 (M+H).

Workup

  1. customThe solvents were removed under reduced pressure
  2. customthe residue was purified by chromatography on silica gel (75% EtOAc/hexane)
  3. customto give the intermediate Boc-
  4. concentrationThe mixture was then concentrated
  5. customthe residue was purified by Gilson reverse phase HPLC (Aquasil C-18 column, 35-85% MeOH/H2O+HCO2H, 30 min. linear gradient elution)

Sources & evidence

ORD record
ord-e935b5877a234a63a3c5f409614fdc10
Source dataset
uspto-grants-2013_03
Patent number
US08404846B2

Reaction notes

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