Water → Methyl 2-chloroquinazoline-7-carboxylate

HRID 1672453Notes

Reaction equation

HRID 1672453 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:8]=2)[N:3]=1.CCN(C(C)C)C(C)C.O>CCOC(C)=O.[Pd]>[Cl:1][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][CH:8]=2)[N:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 81531DiisopropylethylamineHCID 40152337Methyl 2,4-dichloroquinazoline-7-carboxylate

Product 1

HCID 40152338Methyl 2-chloroquinazoline-7-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 2,4-dichloroquinazoline-7-carboxylate (1250 mg, 4.86 mmol) in EtOAc (100 mL) at R.T. was added Hunig's base (0.847 mL, 4.86 mmol) to form a pale yellow solution. The Pd catalyst was added and the mix hydrogenated with a H2 balloon for 1 hour. Water (20 mL) was added to solubilize salts, and mix filtered to remove Pd. The aqueous layer separated and organics dried over MgSO4, filtered and stripped to yield a residue (yellow solid) that was purified by Biotage 40M chromatography (loaded in DCM) eluting with 15-60% EtOAc/Hex over 2000 mL to afford the title compound as a pale yellow solid, 724 mg, 67%. 1H NMR (400 MHz, DMSO-D6) δ ppm 9.75 (1H, s) 8.45 (1H, s) 8.37 (1H, d, J=8.34 Hz) 8.13-8.30 (1H, m) 3.96 (3H, s); MS (API+) for C10H7N2ClO2 m/z 223.1 (M+H)+.

Workup

  1. customto form a pale yellow solution
  2. additionmix
  3. filtrationfiltered
  4. customto remove Pd
  5. customThe aqueous layer separated
  6. dry with materialorganics dried over MgSO4
  7. filtrationfiltered
  8. customto yield a residue (yellow solid) that
  9. customwas purified by Biotage 40M chromatography (loaded in DCM)
  10. washeluting with 15-60% EtOAc/Hex over 2000 mL

Sources & evidence

ORD record
ord-820146ba4f5942b990e59a315dace10c
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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