Potassium Carbonate → N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(pyrrolidin-1-yl)ethoxy]quinazolin-4-amine

HRID 1838532

반응식

HRID 1838532 반응식
Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:3][CH2:4][N:5]4[CH2:9][CH2:8][CH2:7][CH2:6]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochloride2회HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

생성물 1

HCID 5329018N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(pyrrolidin-1-yl)ethoxy]quinazolin-4-amine수율 10%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

1-(2-Chloroethyl)pyrrolidine hydrochloride (200 mg, 1.2 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (403 mg, 1.26 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (650 mg, 4.7 mmol) in DMF (4 ml). The mixture was heated to 100° C. and further portions of 1-(2-chloroethyl)pyrrolidine hydrochloride (800 mg in total) were added periodically over 4 hours while the reaction mixture was maintained at 100° C. The reaction was then allowed to cool and volatiles were removed by evaporation. The residue was partitioned between methylene chloride and water, separated and the organic phase passed through phase separating paper. Column chromatography eluting with methylene chloride/methanol (95/5) gave 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl) ethoxy)quinazoline (50 mg, 10%).

후처리

  1. custom(prepared
  2. temperaturewas maintained at 100° C
  3. temperatureto cool
  4. customvolatiles were removed by evaporation
  5. customThe residue was partitioned between methylene chloride and water
  6. customseparated
  7. customseparating paper
  8. washColumn chromatography eluting with methylene chloride/methanol (95/5)

출처 및 근거

ORD 기록
ord-39b32b474e5d40449056596648b5e890
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06673803B2

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