Diiodomethane → Methyl 5-fluoro-2-iodoquinazoline-7-carboxylate

HRID 715080Notes

Reaction equation

HRID 715080 reaction equation
N[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][C:8]=2[F:12])[N:3]=1.[I:17]CI.N(OCCC(C)C)=O>C1COCC1.CCOC(C)=O.[Cu]I>[F:12][C:8]1[CH:7]=[C:6]([C:13]([O:15][CH3:16])=[O:14])[CH:5]=[C:4]2[C:9]=1[CH:10]=[N:11][C:2]([I:17])=[N:3]2

Participants

7

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 71247028Methyl 2-amino-5-fluoroquinazoline-7-carboxylate

Product 1

HCID 71744098Methyl 5-fluoro-2-iodoquinazoline-7-carboxylateYield 55.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of methyl 2-amino-5-fluoro-quinazoline-7-carboxylate (4.28 g, 19.3 mmol, 1.00 equiv), CuI (1.81 g, 9.5 mmol, 0.49 equiv) and diiodomethane (7.80 mL, 96.8 mmol, 5.0 equiv) in THF (80 ml) was treated with isoamyl nitrite (7.80 mL, 58.1 mmol, 3.00 equiv) at ambient temperature, and the mixture heated to 60 ° C. After 18 h the reaction was cooled. The mixture was diluted with EtOAc (100 mL), filtered through a Celite® pad, and the dark green filtrate concentrated in vacuo to an oily residue (23.0 g) which was absorbed onto SiO2 and purified by flash chromatography eluting with an EtOAc/heptane gradient (0 to 30% EtOAc) to afford 3.54 g (55%) of methyl 5-fluoro-2-iodoquinazoline-7-carboxylate as a cream-white solid: 1H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 8.49 (s, 1H), 7.90 (d, J=9.5 Hz, 1H), 4.02 (s, 3H); LCMS: MH+333.0

Workup

  1. temperatureAfter 18 h the reaction was cooled
  2. filtrationfiltered through a Celite® pad
  3. concentrationthe dark green filtrate concentrated in vacuo to an oily residue (23.0 g) which
  4. customwas absorbed onto SiO2
  5. custompurified by flash chromatography
  6. washeluting with an EtOAc/heptane gradient (0 to 30% EtOAc)

Sources & evidence

ORD record
ord-80e67c025f704728a20b4fbfae5638b9
Source dataset
uspto-grants-2015_11
Patent number
US09187462B2

Reaction notes

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