N,N-Bis(trimethylsilyl)trifluoroacetamide → 2-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-4-thiazolecarboxylic acid, ethyl ester

HRID 1275878Notes

Reaction equation

HRID 1275878 reaction equation
[CH:1]1[C:11]2[CH:10]=[CH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([C:16]3[C:17](=[O:23])[NH:18][C:19](=[O:22])[NH:20][CH:21]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C[Si](N([Si](C)(C)C)C(=O)C(F)(F)F)(C)C.Br[CH2:40][C:41]1[S:42][CH:43]=[C:44]([C:46]([O:48][CH2:49][CH3:50])=[O:47])[N:45]=1>ClCCCl.C(#N)C>[CH:1]1[C:11]2[CH:10]=[CH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([C:16]3[C:17](=[O:23])[NH:18][C:19](=[O:22])[N:20]([CH2:40][C:41]4[S:42][CH:43]=[C:44]([C:46]([O:48][CH2:49][CH3:50])=[O:47])[N:45]=4)[CH:21]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 65279N,N-Bis(trimethylsilyl)trifluoroacetamideHCID 11043146Ethyl 2-(bromomethyl)-1,3-thiazole-4-carboxylateHCID 110986755-(5h-Dibenzo[a,d]cyclohepten-5-yl)-2,4(1h,3h)-pyrimidinedione

Product 1

HCID 117334062-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-4-thiazolecarboxylic acid, ethyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6342AcetonitrileSolvent

Procedure

To a slurry of the product of step (iii) (1.1 g) in dry 1,2-dichloroethane (20 ml) was added bis(trimethylsilyl)trifluoroacetamide (1.9 ml) under nitrogen. The mixture was heated under reflux for 1 hour until the mixture became a homogeneous solution. The solution was allowed to cool to room temperature and a solution of the product of step (ii) (0.83 g) in dry acetonitrile (10 ml) was added. The solution was then heated at reflux for 7 hours. The reaction mixture was allowed to cool and evaporated under reduced pressure. Purification was by chromatography eluting with 30% ethyl acetate in toluene. The resulting oil was triturated with diethyl ether/isohexane to give the product as a cream solid. Yield 1.52 g.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 1 hour until the mixture
  3. temperatureThe solution was then heated
  4. temperatureat reflux for 7 hours
  5. temperatureto cool
  6. customevaporated under reduced pressure
  7. customPurification
  8. washeluting with 30% ethyl acetate in toluene
  9. customThe resulting oil was triturated with diethyl ether/isohexane

Sources & evidence

ORD record
ord-cbfdeb02c02d4b3e88f03eecc472b0af
Source dataset
uspto-grants-2000_12
Patent number
US06162808

Reaction notes

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