Tetrahydrofuran → 2-(2-Chloro-4-morpholino-quinazolin-7-yl)propan-2-ol

HRID 517477Notes

Reaction equation

HRID 517477 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]([N:12]2CCOCC2)[C:9]2[C:4](=[CH:5][C:6](C(OC)=O)=[CH:7][CH:8]=2)[N:3]=1.[CH2:22]1[CH2:26][O:25][CH2:24][CH2:23]1.[CH3:27][Mg]Br.C([O:33][CH2:34][CH3:35])(=O)C>>[Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:22][CH2:26][O:25][CH2:24][CH2:23]2)[C:9]2[C:4](=[CH:5][C:6]([C:34]([OH:33])([CH3:35])[CH3:27])=[CH:7][CH:8]=2)[N:3]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 87428384Methyl 2-chloro-4-morpholino-quinazoline-7-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 874287062-(2-Chloro-4-morpholino-quinazolin-7-yl)propan-2-olYield 56%

Conditions

Temperature
0 °C

Procedure

To a 25 mL round bottom flask, methyl 2-chloro-4-morpholino-quinazoline-7-carboxylate (0.5 g, 0.001628 mol; prepared as described in Example 7; Scheme 8A) and anhydrous THF were added and cooled to 0° C. To the flask was added methyl magnesium bromide (4.65 ml of 1.4 M in diethyl ether, 0.006514 mol) drop wise at 0° C. and the reaction mixture was stirred at room temperature for 12 h. The reaction mass was diluted with ethyl acetate and washed with water. The ethyl acetate layer was dried over anhydrous sodium sulfate and evaporated under reduced to get the crude product. The crude product was purified by column chromatography using 60-120 silica gel and 50% ethyl acetate in hexane to yield the title compound [0.28 g, 56%]. 1H NMR (300 MHz, CDCl3): δ 7.85 (d, J=1.8 Hz, 1H), 7.87 (d, J=8.7 Hz 1H), 7.64 (dd, J′=2.1, J″=8.7 Hz, 1H), 3.87 (s, 8H), 1.63 (s, 6H). LC-MS (ESI): Calculated mass: 307.78; Observed mass: 308.1 (RT: 0.42 min).

Workup

  1. washwashed with water
  2. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  3. customevaporated
  4. customto get the crude product
  5. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-dbfa2221138b448b8fd77fd78b43402d
Source dataset
uspto-grants-2015_08
Patent number
US09115092B2

Reaction notes

Loading…