Ethyl isocyanate → N-(2-chlorophenyl)-8-(3-ethylureido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

HRID 1949739Notes

Reaction equation

HRID 1949739 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[CH:5][C:6]2[C:12]3[S:13][C:14]([C:16]([N:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[Cl:26])[CH3:19])=[O:17])=[CH:15][C:11]=3[CH2:10][CH2:9][O:8][C:7]=2[CH:27]=1.CCN(C(C)C)C(C)C.[CH2:37]([N:39]=[C:40]=[O:41])[CH3:38].[Cl-].[NH4+]>C1COCC1>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[N:18]([CH3:19])[C:16]([C:14]1[S:13][C:12]2[C:6]3[CH:5]=[CH:4][C:3]([NH:2][C:40]([NH:39][CH2:37][CH3:38])=[O:41])=[CH:27][C:7]=3[O:8][CH2:9][CH2:10][C:11]=2[CH:15]=1)=[O:17]

Participants

6

Reactant 4

HCID 8022Ethyl isocyanateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 66868531HCID 66868531, compound

Product 1

HCID 44242563N-(2-chlorophenyl)-8-(3-ethylureido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamideYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 8-amino-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide HCl salt (0.25 g, 0.593 mmol) in anhydrous THF (15 mL) was added DIPEA (0.52 mL, 2.97 mmol) and ethyl isocyanate (0.1 g, 1.4 mmol). The solution was stirred at 40° C. overnight. The reaction mixture was poured into ammonium chloride aqueous solution and extracted with EtOAc. The organic phase was washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated to the crude product, which was purified by preparative TLC to afford about 0.113 g of 166 (isolated yield: 42%). 1H NMR (DMSO-d6, 400 MHz): δ 8.56 (s, 1H), 7.64-7.58 (m, 2H), 7.49 (t, J=3.6 Hz, 2H), 7.22 (d, J=4.4 Hz, 1H), 7.15 (d, J=2.4 Hz, 1H), 6.92 (dd, J=2.0, 8.4 Hz, 1H), 6.44 (s, 1H), 6.13 (t, J=5.6 Hz, 1H), 4.09 (d, J=4.4 Hz, 2H), 3.22 (s, 3H), 3.06 (dd, J=6.0, 7.2 Hz, 2H), 2.85 (s, 2H), 1.01 (t, J=7.2 Hz, 3H). MS: (ESI+) 456.1

Workup

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated to the crude product, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-15bfc30998694d6bbfab48064b3a16a6
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Reaction notes

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