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

HRID 2205310
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HRID 2205310 반응식
[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]
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참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide
용매
2회

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온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-df13fb3652dc4a2eb3764d026b5fd41c
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09371292B2

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