Pyridine → HCID 15521320, compound

HRID 1975973Notes

Reaction equation

HRID 1975973 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][NH:6][C:5]2=O.C(Cl)(=O)C(Cl)=O.N1C=CC=CC=1.ClC1C2C(=CC=C(I)C=2)N=CN=1.[NH2:37][C:38]1[CH:39]=[C:40]2[C:44](=[CH:45][CH:46]=1)[NH:43][CH:42]=[CH:41]2>C(Cl)Cl.CN(C=O)C.C(Cl)(Cl)Cl.C(O)(C)(C)C>[NH:43]1[C:44]2[C:40](=[CH:39][C:38]([NH:37][C:5]3[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([I:1])[CH:3]=4)[N:8]=[CH:7][N:6]=3)=[CH:46][CH:45]=2)[CH:41]=[CH:42]1

Participants

10

Reactant 5

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 788675-AminoindoleHCID 111738094-Chloro-6-iodoquinazolineHCID 1354016666-Iodoquinazolin-4-one

Product 1

HCID 15521320HCID 15521320, compoundYield 42.3%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
60 °C

Procedure

6-Iodo-3H-quinazolin-4-one (50 gm, 18.3 mmol) was slurried in 60 mL methylene chloride (CH2Cl2) with several drops of DMF. Oxalyl chloride (6.99 g, 4.83 mL, 55.1 mmol) was added dropwise to the slurry at 0° C. The reaction was refluxed for 48 hours and then concentrated in vacuo. Pyridine (2.9 gm, 2.97 mL, 36.7 mmol) and tert-butyl alcohol (10 mL) was added to dissolve the 4-chloro-6-iodo quinazoline. 5-Aminoindole (2.9 gm, 22.0 mmol) was added and the reaction was heated to 60° C. overnight. Diluted the reaction mixture with chloroform (CHCl3) and washed with brine, saturated aqueous NaCHO3 and dried over NaSO4. The organic layer was concentrated in vacuo to a black oil. The crude product was chromatographed on silica gel (2 parts methanol to 1 part methylene chloride (2 MeOH/CH2Cl2)) to provide 2.99 gm of white crystalline product.

Workup

  1. temperatureThe reaction was refluxed for 48 hours
  2. concentrationconcentrated in vacuo
  3. washwashed with brine, saturated aqueous NaCHO3
  4. dry with materialdried over NaSO4
  5. concentrationThe organic layer was concentrated in vacuo to a black oil
  6. customThe crude product was chromatographed on silica gel (2 parts methanol to 1 part methylene chloride (2 MeOH/CH2Cl2))

Sources & evidence

ORD record
ord-77d1ced2e5c0417ca1410fa3169fc089
Source dataset
uspto-grants-2001_05
Patent number
US06225318B1

Reaction notes

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