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

HRID 1483199Notes

Reaction equation

HRID 1483199 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.[NH2:11][C:12]1[S:27][C:15]2[CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19][C:14]=2[C:13]=1[C:28](=[O:30])[NH2:29].C(N(CC)CC)C>O1CCCC1>[C:28]([C:13]1[C:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:16][C:15]=2[S:27][C:12]=1[NH:11][C:9]([NH:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:10])(=[O:30])[NH2:29]

Participants

5

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 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-chlorophenyl isocyanate (11.1 g, 72.3 mmol), compound A2 (19.5 g, 65.6 mmol), and triethylamine (12.0 mL, 86.1 mmol) in anhydrous tetrahydrofuran (150 mL) was stirred at room temperature for 16 h. After this time, the reaction mixture was concentrated under reduced pressure. The resulting residue was triturated with a mixture of 1:1 methylene chloride and ethyl acetate to afford compound A3 as an off-white solid (25.3 g, 86%): 1H NMR (300 MHz, DMSO-d6) δ 10.85 (s, 1H), 10.20 (s, 1H), 7.52-7.45 (m, 3H), 7.34 (d, J=9.0 Hz, 2H), 6.94 (bs, 1H), 4.43 (s, 2H), 3.57-3.53 (m, 2H), 2.79-2.75 (m, 2H), 1.43 (s, 9H). MS (M+Na) 473.

Workup

  1. concentrationAfter this time, the reaction mixture was concentrated under reduced pressure
  2. customThe resulting residue was triturated with a mixture of 1:1 methylene chloride and ethyl acetate

Sources & evidence

ORD record
ord-ce1133f9834d4236b374bec7deb89021
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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