Thiourea → [2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine

HRID 1186117Notes

Reaction equation

HRID 1186117 reaction equation
[CH3:1][S:2][C:3]1[N:4]=[C:5](O)[C:6]2[CH2:12][CH2:11][N:10]([C:13]3[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:9][CH2:8][C:7]=2[N:23]=1.C(OC(C1C(=O)CCN([C:38]2[C:43]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:41]=[CH:40][N:39]=2)CC1)=O)C.[CH3:48]C[O-].[Na+].NC(N)=S>CCO>[CH3:1][S:2][C:3]1[N:4]=[C:5]([NH:39][C:40]2[CH:41]=[CH:42][C:43]([C:44]([F:45])([F:46])[F:47])=[CH:38][CH:48]=2)[C:6]2[CH2:12][CH2:11][N:10]([C:13]3[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:9][CH2:8][C:7]=2[N:23]=1

Participants

6

Reactant 4

HCID 2723790ThioureaHCID 2723922Sodium ethoxideHCID 589727845-Oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl esterHCID 178503519HCID 178503519, compound

Product 1

HCID 58972614[2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amineYield 99%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ol. To solution of 5-oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl ester (3.0 g, 9.09 mmol) in EtOH (40 mL) was added NaOEt (1.97 g, 29.1 mmol) and thiourea (1.1 g, 13.6 mmol). The mixture was heated at reflux for 12 h. The mixture was cooled, treated with Mel (0.74 mL, 11.8 mmol) drop-wise, and stirred at rt for 1 h. Thee mixture was concentrated and the residue was dissolved in water and acidified to pH=7 with HOAc (a precipitate formed). The solid was filtered to give the title compound (3.3 g, >99%), which was used in the next step without further purification.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 12 h
  3. temperatureThe mixture was cooled
  4. additiontreated with Mel (0.74 mL, 11.8 mmol) drop-wise
  5. concentrationThee mixture was concentrated
  6. dissolutionthe residue was dissolved in water
  7. customformed)
  8. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-6743218b00ef48dea92c6852e3d72ea6
Source dataset
uspto-grants-2014_03
Patent number
US08673895B2

Reaction notes

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