Dichloromethane → HCID 136379428, compound

HRID 2400432Notes

Reaction equation

HRID 2400432 reaction equation
C(N=C=NC(C)C)(C)C.[CH3:10][C:11]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24](OCC)=[O:25])=S)=[CH:16][C:15]=1[F:29].[NH:35]1[CH:39]=[C:38]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH:37]=[N:36]1.C(Cl)Cl>ClCCCl.Cl[Ti](Cl)(Cl)Cl.CCO>[CH3:10][C:11]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:12]=1[O:13][C:14]1[CH:19]=[C:18]2[C:17](=[CH:16][C:15]=1[F:29])[N:20]=[C:21]([N:35]1[CH:39]=[C:38]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH:37]=[N:36]1)[NH:23][C:24]2=[O:25]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 12734DiisopropylcarbodiimideHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 86686094HCID 86686094, compound

Product 1

HCID 136379428HCID 136379428, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 111,2-DichloroethaneSolventHCID 702EthanolSolvent

Procedure

Neat diisopropylcarbodiimide (45.4 g, 290 mmol) was added to a solution of 1-(4-(2,6-dimethylphenoxy)-3-fluorophenyl)-3-ethoxycarbonylthiourea (100 g, 276 mmol), ethyl pyrazole-4-carboxylate (45.4 g, 290 mmol), and DCM (1 L). The solution was maintained at rt for 24 h, then concentrated. The residue was stirred with ether (500 mL) for 3 h in an ice bath, then filtered. The filtrate was concentrated to a thick orange oil (180 g, ca. 70% purity, 97%). A portion of this material (20 g, ca. 30 mmol) was dissolved in DCE (150 mL), then neat TiCl4 was added. The mixture was then heated to reflux for 6 h, then cooled in an ice bath. EtOH (750 mL) was added, and the mixture was stirred for 3 h. The resulting precipitate was collected by filtration, washed with cold EtOH, and dried to provide the titled compound (3.9 g, 31%). 1H NMR (500 MHz, DMSO): 13.03 (s, 1H), 8.95 (d, J=0.6 Hz, 1H), 8.29 (s, 1H), 7.75 (d, J=11.5 Hz, 1H), 7.31-7.24 (m, 2H), 7.22 (dd, J=8.5, 6.4 Hz, 1H), 6.96 (d, J=9.1 Hz, 1H), 4.29 (q, J=7.1 Hz, 2H), 2.11 (s, 6H), 1.32 (t, J=7.1 Hz, 3H).

Workup

  1. concentrationconcentrated
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated to a thick orange oil (180 g, ca. 70% purity, 97%)
  4. temperatureThe mixture was then heated
  5. temperatureto reflux for 6 h
  6. temperaturecooled in an ice bath
  7. stirringthe mixture was stirred for 3 h
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed with cold EtOH
  10. customdried

Sources & evidence

ORD record
ord-5a71ff5af25a4ae59a97aa3af7a284b2
Source dataset
uspto-grants-2014_08
Patent number
US08796263B2

Reaction notes

Loading…