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

HRID 56360ノート

反応式

HRID 56360 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

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

反応条件

温度
100 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-928af81ecb674aee8d539c1746e1a5ab
出典データセット
uspto-grants-2016_09
特許番号
US09434700B2

反応ノート

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