Phenylacetyl isothiocyanate → 7-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-N-(pyrrolidin-3-yl)thieno[3,2-b]pyridine-2-carboxamide

HRID 1711059Notes

Reaction equation

HRID 1711059 reaction equation
[NH2:1][C:2]1[CH:32]=[CH:31][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]([NH:18][CH:19]4[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]4)=[O:17])[S:15][C:8]=23)=[C:4]([F:33])[CH:3]=1.[C:34]1([CH2:40][C:41]([N:43]=[C:44]=[S:45])=[O:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C1COCC1.C(O)(C(F)(F)F)=O.C(Cl)Cl>[F:33][C:4]1[CH:3]=[C:2]([NH:1][C:44]([NH:43][C:41](=[O:42])[CH2:40][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[S:45])[CH:32]=[CH:31][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]([NH:18][CH:19]3[CH2:23][CH2:22][NH:21][CH2:20]3)=[O:17])[S:15][C:8]=12

Participants

5

Reactant 2

HCID 12454157Phenylacetyl isothiocyanateHCID 59424462tert-Butyl 3-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridine-2-carboxamido)pyrrolidine-1-carboxylate

Product 1

HCID 594244267-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-N-(pyrrolidin-3-yl)thieno[3,2-b]pyridine-2-carboxamideYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of 290 (40 mg, 0.084 mmol) and 2-phenylacetyl isothiocyanate (22 mg, 0. 126 mmol) in THF (2 mL) was stirred for 30 min. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (eluent EtOAc), to afford a solid material, which was dissolved in a mixture of TFA/DCM (0.5 mL/0.5 mL) and stirred at room temperature for 2 h. Solvents were removed under reduced pressure and the residue was purified by preparative HPLC (Aqusil C18, gradient eluent, 60-95% MeOH in water, 45 min) to afford the title compound 291 (8 mg, 80% yield) as an off-white solid. 1H NMR (d-DMSO) δ (ppm): 9.27(d, 1H), 8.57(d, 1H), 8.37 (s, 1H), 8.30 (s, 1H), 8.01(d, 1H), 7.53 (m, 2H), 7.33-7.31 (m, 4H), 7.29-7.25 (m, 1H), 6.74(d, 1H), 4.46 (m, 1H), 3.82 (s, 2H), 3.11-3.03 (m, 2H), 2.18-2.09 (m, 2H), 1.93-1.89 (m, 2H). MS (m/z): 550.2 (M+H) (found).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by flash column chromatography (eluent EtOAc)
  3. customto afford a solid material, which
  4. customSolvents were removed under reduced pressure
  5. customthe residue was purified by preparative HPLC (Aqusil C18, gradient eluent, 60-95% MeOH in water, 45 min)

Sources & evidence

ORD record
ord-b4e9b354322140949c5e6339101474f4
Source dataset
uspto-grants-2010_09
Patent number
US07790729B2

Reaction notes

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