4-Chlorophenyl Isocyanate → tert-Butyl 3-carbamoyl-2-[3-(4-chlorophenyl)ureido]-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate

HRID 1483223Notes

Reaction equation

HRID 1483223 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.C(N(CC)CC)C.[NH2:18][C:19]1[S:34][C:22]2[CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26][C:21]=2[C:20]=1[C:35](=[O:37])[NH2:36]>C1COCC1.C(Cl)Cl>[C:35]([C:20]1[C:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH2:23][C:22]=2[S:34][C:19]=1[NH:18][C:9]([NH:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:10])(=[O:37])[NH2:36]

Participants

6

Reactant 3

HCID 76934-Chlorophenyl IsocyanateHCID 8471TriethylamineHCID 50873949tert-Butyl 2-amino-3-carbamoyl-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate

Product 1

HCID 66662753tert-Butyl 3-carbamoyl-2-[3-(4-chlorophenyl)ureido]-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylateYield 66.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-chlorophenyl isocyanate (325 mg, 2.12 mmol) and triethylamine (444 μL, 3.18 mmol) in anhydrous THF (10 mL) was added tert-butyl 2-amino-3-carbamoyl-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate (632 mg, 2.12 mmol) and the reaction mixture was stirred at rt for 8 h. The reaction mixture was concentrated in vacuo to afford oil, which was taken up in DCM and washed with water (×2). The organics were then dried with anhydrous Na2SO4 and concentrated in vacuo. The product was purified by Isolera system (SiO2 gel as stationary phase, 25 g HP column, dry loading) using DCM-DCM/MeOH (0%-8% MeOH in DCM) to afford the title compound as a tan solid (633 mg, 57% yield). LRMS [M+H]451.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto afford oil, which
  3. washwashed with water (×2)
  4. dry with materialThe organics were then dried with anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by Isolera system (SiO2 gel as stationary phase, 25 g HP column, dry loading)

Sources & evidence

ORD record
ord-5be04b22e5a94dce97d04de00566e700
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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