Potassium Phosphate, Tribasic → tert-butyl ((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate

HRID 56360노트

반응식

HRID 56360 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][C@@H:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[N:6]=[CH:5]2.[Cl:26][C:27]1[C:32]([O:33][CH2:34][CH3:35])=[CH:31][CH:30]=[C:29]([F:36])[C:28]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[Cl:26][C:27]1[C:32]([O:33][CH2:34][CH3:35])=[CH:31][CH:30]=[C:29]([F:36])[C:28]=1[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][C@@H:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:24])[CH3:22])[N:6]=[CH:5]2

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 445581442-Chloro-3-ethoxy-6-fluorophenylboronic acidHCID 118043383tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate

생성물 1

HCID 118043384tert-butyl ((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate수율 84.8%

시약·촉매·용매 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
100 °C

실험 절차

A mixture of tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate (50 mg, 0.12 mmol), (2-chloro-3-ethoxy-6-fluorophenyl)boronic acid (40 mg, 0.18 mmol), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (4 mg, 0.005 mmol) and potassium phosphate (78 mg, 0.37 mmol) in 1,4-dioxane/water (1.15 mL/0.15 mL) was degassed with nitrogen for 5 min and stirred at 100° C. for 30 min under microwave. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with saturated ammonium chloride solution and dried with sodium sulfate. The residue was purified by silica gel column chromatography to afford tert-butyl ((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate (51 mg, 83%). MS (ES+) C26H30ClFN4O3 requires: 500, found: 501 [M+H]+.

후처리

  1. customwas degassed with nitrogen for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washwashed with saturated ammonium chloride solution
  5. dry with materialdried with sodium sulfate
  6. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-928af81ecb674aee8d539c1746e1a5ab
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434700B2

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