Trifluoroacetic acid → HCID 178489995, compound

HRID 1627270Notes

Reaction equation

HRID 1627270 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:35])[C:8]=1[CH2:9][S:10][C:11]1[N:12]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:13]([C:16]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([O:26][CH3:27])[CH:20]=2)([CH3:18])[CH3:17])=[CH:14][N:15]=1)[NH2:5].Cl[C:37](Cl)([O:39]C(=O)OC(Cl)(Cl)Cl)Cl.CCN(CC)CC.[NH2:55][C@H:56]([C:64]([OH:66])=[O:65])[CH2:57][CH2:58][CH2:59][NH:60][C:61](=[NH:63])[NH2:62].C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:37](=[O:39])[NH:55][C@@H:56]([CH2:57][CH2:58][CH2:59][NH:60][C:61]([NH2:62])=[NH:63])[C:64]([OH:66])=[O:65])[CH:6]=[C:7]([F:35])[C:8]=1[CH2:9][S:10][C:11]1[N:12]([C:28]2[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=2)[C:13]([C:16]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([O:26][CH3:27])[CH:20]=2)([CH3:17])[CH3:18])=[CH:14][N:15]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 94429TriphosgeneHCID 66739983HCID 66739983, compoundHCID 178418600HCID 178418600, compound

Product 1

HCID 178489995HCID 178489995, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluoroaniline (175 mg, 0.322 mmol) in CHCl3 (10 mL) was added triphosgene (97 mg, 0.322 mmol) followed by Et3N (227.6 mg, 2.254 mmol) at 0° C. The mixture was stirred at room temperature 20 min. PMC protected L-arginine was added to the reaction mixture and allowed to stir at the same temperature overnight. Purification by column chromatography provided the protected product. Deprotection was performed by stirring with TFA (2 mL) and DCM (2 mL) for 1 h. Purification on HPLC yielded the title compound (52 mg). 1H NMR (400 MHz, MeOD) δ 7.24 (s, 1H), 7.26-7.12 (m, 3H), 6.81 (d, J=8.7 Hz, H), 6.79 (d, J=8.7 Hz, 1H), 6.54-6.48 (m, 2H), 6.25-6.14 (m, 2H), 4.22 (t, J=5.7 Hz, 1H), 3.97 (s, 2H), 3.68 (s, 3H), 3.23 (dt, J=13.6, 6.7 Hz, 2H), 2.08-1.77 (m, 4H), 1.53 (s, 6H); MS (EI) m/z 734 (MH+).

Workup

  1. additionwas added to the reaction mixture
  2. stirringto stir at the same temperature overnight
  3. customPurification by column chromatography
  4. customprovided the protected product
  5. customPurification on HPLC

Sources & evidence

ORD record
ord-70c427cc790647ad85b6f4a5b7581d92
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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