Methanol → 2,4-Quinazolinediamine, 5-methoxy-

HRID 2276827Notes

Reaction equation

HRID 2276827 reaction equation
CO.[H-].[Na+].F[C:6]1[CH:13]=[CH:12][CH:11]=[C:10](F)[C:7]=1[C:8]#[N:9].[C:15](=O)(O)[OH:16].[NH2:19][C:20]([NH2:22])=[NH:21]>O1CCCC1.CN(C)C(=O)C.O>[CH3:15][O:16][C:6]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:7]=1[C:8]([NH2:9])=[N:21][C:20]([NH2:22])=[N:19]2

Participants

8

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 746952,6-DifluorobenzonitrileHCID 286947Carbonic acid-guanidine (1:1)

Product 1

HCID 2137522,4-Quinazolinediamine, 5-methoxy-Yield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

2.53 g (79.08 mmol) of methanol was dropped into 5.18 g (86.27 mmol) of 40% sodium hydride suspension in tetrahydrofuran (150 ml) at 0° C. and stirred for 10 min, followed by dropwise addition of 10.0 g (71.89 mmol) of 2,6-difluorobenzonitrile in tetrahydrofuran (100 ml). The reaction mixture as stirred at room temperature for 10 h to complete the reaction. 200 ml of water was added thereto to destroy the excess sodium hydride, and the reaction mixture was extracted with 500 ml of ethyl acetate. The organic layer was dried with anhydrous sodium sulfate and evaporated to dryness. The residue was passed through column chromatography to provide an intermediate. The intermediate and 17.41 g (143.78 mmol) of guanidine carbonate were heated to 140° C. in 300 ml of N,N-dimethylacetamide and stirred for 8 h to complete the reaction. The reaction mixture was evaporated to dryness, then diluted with 200 ml of water and extracted with 400 ml of dichloromethane. The organic layer was dried with anhydrous sodium sulfate and then evaporated to dryness. The residue was passed through column chromatography to proved 9.85 g of compound Yhhu-0967 with a total yield of 72% in the two steps).

Workup

  1. stirringThe reaction mixture as stirred at room temperature for 10 h
  2. customthe reaction
  3. customto destroy the excess sodium hydride
  4. extractionthe reaction mixture was extracted with 500 ml of ethyl acetate
  5. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  6. customevaporated to dryness
  7. customto provide an intermediate
  8. stirringstirred for 8 h
  9. customthe reaction
  10. customThe reaction mixture was evaporated to dryness
  11. additiondiluted with 200 ml of water
  12. extractionextracted with 400 ml of dichloromethane
  13. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  14. customevaporated to dryness

Sources & evidence

ORD record
ord-a21b84bf9ec74bc0a568b38893d51b37
Source dataset
uspto-grants-2015_09
Patent number
US09133138B2

Reaction notes

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