Morpholine → 2-Chloro-4-morpholino-6-fluoro-7-bromo-quinazoline

HRID 2284398Notes

Reaction equation

HRID 2284398 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](Cl)=[N:7][C:8]([Cl:12])=[N:9]2)=[CH:4][C:3]=1[F:14].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>ClCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[N:7][C:8]([Cl:12])=[N:9]2)=[CH:4][C:3]=1[F:14]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 866657637-Bromo-2,4-dichloro-6-fluoroquinazoline

Product 1

HCID 866657622-Chloro-4-morpholino-6-fluoro-7-bromo-quinazolineYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice cold solution of 7-bromo-2,4-dichloro-6-fluoro-quinazoline (0.35 g, 1.178 mmol) in dichloromethane (15 mL), morpholine (0.566 mL, 0.0066 mol) was slowly added and the reaction was continued for 20 minutes. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulphate and evaporated to provide crude solid. The crude material was purified using column chromatography (60-120 silica gel, 30% ethyl acetate in hexane) to provide the title compound (220 mg, 57%). 1H NMR (300 MHz, DMSO-d6): δ 8.16 (d, J=6.6 Hz, 1H), 8.01 (d, J=9.6 Hz, 1H), 3.83-3.86 (m, 4H), 3.76-3.73 (m, 4H); LC-MS (ESI): Calculated mass: 345.0; Observed mass [M+H]+: 347.8 (RT: 1.70 min).

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. customevaporated
  4. customto provide crude solid
  5. customThe crude material was purified

Sources & evidence

ORD record
ord-40fd101792e74b128f2455dd0a57971f
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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