Iodine → ethyl 8-iodo-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

HRID 81946

Reaction equation

HRID 81946 reaction equation
N[C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:13][N:14]([CH3:15])[C:5]=3[C:4]=2[N:3]=1.[I-:21].[Cs+].II.N(OCCC(C)C)=O>C(COC)OC.[Cu](I)I>[I:21][C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:13][N:14]([CH3:15])[C:5]=3[C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 807IodineHCID 8053Isoamyl NitriteHCID 24601Cesium iodideHCID 24993827ethyl 8-amino-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

Product 1

HCID 44232943ethyl 8-iodo-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylateYield 46%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a well stirred suspension of ethyl 8-amino-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate (9.0 g, 33 mmol) in dimethoxyethane (0.7 L) under N2, cesium iodide (8.6 g, 33 mmol), bisublimated iodine (4.19 g, 16.5 mmol), copper iodide (2.0 g, 10 mmol) and isopentyl nitrite (6.62 mL, 49.5 mmol) were added in sequence. The reaction mixture was stirred vigorously at 65-70° C. for 3 hours. After cooling in an ice-water bath, the solid was filtered off. The filtrate was diluted with dichloromethane (2.0 L), washed with 30% ammonium hydroxide (150 mL), sodium thiosulphate (300 mL), brine, dried over anhydrous Na2SO4 and concentrated to give 5.69 g of the title compound (46% yield).

Workup

  1. stirringThe reaction mixture was stirred vigorously at 65-70° C. for 3 hours
  2. temperatureAfter cooling in an ice-water bath
  3. filtrationthe solid was filtered off
  4. additionThe filtrate was diluted with dichloromethane (2.0 L)
  5. washwashed with 30% ammonium hydroxide (150 mL), sodium thiosulphate (300 mL), brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-bc92d3892c64466fa8b33352c03f5173
Source dataset
uspto-grants-2014_09
Patent number
US08846701B2

Linked notes

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