Sodium Iodide → HCID 22995793, compound

HRID 1167173Notes

Reaction equation

HRID 1167173 reaction equation
C(N(C(C)C)CC)(C)C.[CH2:10]1[CH:15]2[CH2:16][NH:17][CH2:18][CH2:19][N:14]2[CH2:13][C:12](=[O:20])[O:11]1.FC(F)(F)C(O)=O.[Cl:28][C:29]1[CH:30]=[C:31]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][C:43]([O:52][CH2:53][CH2:54]Br)=[C:44]([O:47][CH2:48][CH:49]4[CH2:51][CH2:50]4)[CH:45]=3)[N:40]=[CH:39][N:38]=2)[CH:32]=[CH:33][C:34]=1[F:35].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C(#N)C>[Cl:28][C:29]1[CH:30]=[C:31]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][C:43]([O:52][CH2:53][CH2:54][N:17]4[CH2:18][CH2:19][N:14]5[CH:15]([CH2:10][O:11][C:12](=[O:20])[CH2:13]5)[CH2:16]4)=[C:44]([O:47][CH2:48][CH:49]4[CH2:51][CH2:50]4)[CH:45]=3)[N:40]=[CH:39][N:38]=2)[CH:32]=[CH:33][C:34]=1[F:35]

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 6422Trifluoroacetic acid2×HCID 11430Potassium Carbonate2×HCID 81531DiisopropylethylamineHCID 18762784HCID 18762784, compoundHCID 22989513Hexahydropyrazino[2,1-c][1,4]oxazin-3(4H)-one2×

Product 1

HCID 22995793HCID 22995793, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

0.25 ml of diisopropylethylamine and 260 mg of perhydro-pyrazino[2,1-c][1,4]oxazin-3-one x 2 trifluoroacetic acid are added to 150 mg of 4-[(3-chloro-4-fluorophenyl)amino]-6-cyclopropylmethoxy-7-(2-bromoethoxy)-quinazoline in 15 ml of acetonitrile. The reaction mixture is stirred for one hour at ambient temperature and then refluxed for two hours. Then 70 mg of potassium carbonate and 75 mg of sodium iodide are added. The reaction mixture is refluxed for about another 14 hours, during which time a total of another 175 mg of perhydro-pyrazino[2,1-c][1,4]oxazin-3-one x 2 trifluoroacetic acid and 300 mg of potassium carbonate are added successively until the reaction is complete. For working up the inorganic salts are filtered off and the filtrate is evaporated down in vacuo. The flask residue is chromatographed over a silica gel column with methylene chloride/methanol (95:5) as eluant. The desired product is obtained as a light brown resin. Yield: 27 mg (16% of theory),

Workup

  1. temperaturerefluxed for two hours
  2. additionare added successively until the reaction
  3. filtrationare filtered off
  4. customthe filtrate is evaporated down in vacuo
  5. customThe flask residue is chromatographed over a silica gel column with methylene chloride/methanol (95:5) as eluant

Sources & evidence

ORD record
ord-c521884d0d0244d5a01a162e44e25c4b
Source dataset
uspto-grants-2003_09
Patent number
US06617329B2

Reaction notes

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