Triethylamine → Diethyl (2-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxy-quinazolin-6-yl)amino)-1-fluoro-2-oxoethyl)phosphonate

HRID 2205310Notes

Reaction equation

HRID 2205310 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=1.C(N(CC)CC)C.Cl[C:31](=[O:42])[CH:32]([P:34](=[O:41])([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37])[F:33]>CN(C=O)C>[Cl:22][C:17]1[CH:16]=[C:15]([NH:14][C:5]2[C:4]3[C:9](=[CH:10][C:11]([O:12][CH3:13])=[C:2]([NH:1][C:31](=[O:42])[CH:32]([P:34](=[O:41])([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37])[F:33])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:20]=[CH:19][C:18]=1[F:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11470313Diethyl (2-chloro-1-fluoro-2-oxoethyl)phosphonateHCID 21847826N4-(3-Chloro-4-fluorophenyl)-7-methoxy-4,6-quinazolinediamine

Product 1

HCID 86727275Diethyl (2-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxy-quinazolin-6-yl)amino)-1-fluoro-2-oxoethyl)phosphonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

6-amino-4-(3-chloro-4-fluorophenylamino)-7-methoxy-quinazoline (1.0 eq.) and triethylamine (1.5 eq.) were dissolved in DMF (10 ml), and the mixture was stirred at 0° C. for 30 min. A solution of diethyl (2-chloro-1-fluoro-2-oxoethyl)phosphonate (1.5 eq.) in DMF (5 ml) was added dropwise slowly into the mixture mentioned above, and stirred overnight at room temperature. After the reaction finished, the mixture was quenched with saturated NaHCO3, extracted with EtOAc, and the organic phase was dried over anhydrous sodium sulfate, concentrated to dryness under reduced pressure, then the crude product was purified by column chromatography (mobile phase 40:1 DCM/MeOH) and a light yellow solid of diethyl (2-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxy-quinazolin-6-yl)amino)-1-fluoro-2-oxoethyl)phosphonate was given. (50% yield).

Workup

  1. stirringstirred overnight at room temperature
  2. customthe mixture was quenched with saturated NaHCO3
  3. extractionextracted with EtOAc
  4. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  5. concentrationconcentrated to dryness under reduced pressure
  6. customthe crude product was purified by column chromatography (mobile phase 40:1 DCM/MeOH)

Sources & evidence

ORD record
ord-df13fb3652dc4a2eb3764d026b5fd41c
Source dataset
uspto-grants-2016_06
Patent number
US09371292B2

Reaction notes

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