Hydrochloric Acid → 7-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-N,N-diisobutylthieno[3,2-b]pyridine-2-carboxamide

HRID 1710904Notes

Reaction equation

HRID 1710904 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([N+:21]([O-])=O)[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14](Cl)=[O:15])[S:13][C:6]=12.[CH2:24]([NH:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:25]([CH3:27])[CH3:26].Cl.[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>C(Cl)Cl.C1COCC1.[Fe].CO>[F:1][C:2]1[CH:20]=[C:19]([NH:21][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:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]([N:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:24][CH:25]([CH3:27])[CH3:26])=[O:15])[S:13][C:6]=12

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8085DiisobutylamineHCID 12454157Phenylacetyl isothiocyanateHCID 594245267-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine-2-carbonyl chloride

Product 1

HCID 866041637-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-N,N-diisobutylthieno[3,2-b]pyridine-2-carboxamideYield 18%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 40 (150 mg, 0.385 mmol) and TEA (107 μl, 0.771 mmol) in anhydrous CH2Cl2 under an atmosphere of nitrogen was added diisobutylamine (67 μL, 0.385 mmol). After stirring for 1 hour, methanol (2 mL) was added followed by iron powder (150 mg) and HCl (conc., 0.4 mL). The reaction mixture was stirred for additional 2 hours and then partitioned between ethyl acetate (20 mL) and a mixture of H2O (20 mL) and NH4OH (2 mL). Organic phase was collected, washed with brine, dried over anhydrous MgSO4, filtered and evaporated. The residue was treated with 2-phenylacetyl isothiocyanate (102 mg, 0.58 mmol) in THF (2 mL), the resultant mixture was allowed to stand for 2 hours at ambient temperature, quenched with methanol (5.0 mL), loaded onto 5 ml of silica gel and purified by flash chromatography using hexane—AcOEt (70:30) as an eluent, to afford title compound 81 (41 mg, 18%) as a white solid. 1H NMR (400 MHz, CD3OD) δ (ppm): 8.54 (d, J=5.6 Hz, 1H), 8.08 (dd, J=2.0 and 12.0 Hz, 1H), 7.69 (s, 1H), 7.38-7.49 (m, 2H), 7.28-7.35 (m, 5H), 6.77 (dd, J=1.2 and 5.6 Hz, 1H), 3.77 (s, 2H), 3.46 (bs, 4H), 2.18 (bs, 1H), 2.02 (bs, 1H), 1.02 (bs, 6H), 0.87 (bs, 6H). LRMS (M+1):592.7 (calcd), 593.3 (found).

Workup

  1. stirringThe reaction mixture was stirred for additional 2 hours
  2. custompartitioned between ethyl acetate (20 mL)
  3. additiona mixture of H2O (20 mL) and NH4OH (2 mL)
  4. customOrganic phase was collected
  5. washwashed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. waitto stand for 2 hours at ambient temperature
  10. customquenched with methanol (5.0 mL)
  11. custompurified by flash chromatography

Sources & evidence

ORD record
ord-9639ecf019034b9ea67f038a13e302f7
Source dataset
uspto-grants-2010_09
Patent number
US07790729B2

Reaction notes

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