Triethylamine → (2E)-4-bromo-N-[4-(3-chloro-4-fluoroanilino)-7-methoxy-6-quinazolinyl]-2-butenamide

HRID 1520727Notes

Reaction equation

HRID 1520727 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.[Br:30][CH2:31]/[CH:32]=[CH:33]/[C:34](Cl)=[O:35]>O1CCCC1>[Br:30][CH2:31]/[CH:32]=[CH:33]/[C:34]([NH:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][C:16]=1[O:21][CH3:22])[N:13]=[CH:12][N:11]=[C:10]2[NH:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)=[O:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11263885(E)-4-Bromo-2-butenoyl ChlorideHCID 21847826N4-(3-Chloro-4-fluorophenyl)-7-methoxy-4,6-quinazolinediamine

Product 1

HCID 66823741(2E)-4-bromo-N-[4-(3-chloro-4-fluoroanilino)-7-methoxy-6-quinazolinyl]-2-butenamideYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of N4-(3-chloro-4-fluorophenyl)-7-methoxy-4,6-quinazolinediamine (8) (4.0 g, 12.5 mmol) in dry tetrahydrofuran (150 mL) under nitrogen was added triethylamine (19 mmol), followed by freshly prepared (2E)-4-bromo-2-butenoyl chloride (15 mmol) in dry tetrahydrofuran (50 mL). The resulting solution was then stirred at room temperature for 2 hours and concentrated under reduced pressure. Trituration from dichloromethane gave crude (2E)-4-bromo-N-[4-(3-chloro-4-fluoroanilino)-7-methoxy-6-quinazolinyl]-2-butenamide (4.6 g) that was used directly.

Workup

  1. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2b8ccc428a684346a6b4e746da0f5c96
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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