Potassium Phosphate, Tribasic → methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid

HRID 56364ノート

反応式

HRID 56364 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.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)[C:31]([OH:33])=[O:32].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:55]1.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>[CH3:55][C:29]1[C:28]([O:27][CH3:26])=[C:36]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([NH:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[NH:18][C:19]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:25])[N:6]=[CH:5]3)[CH:35]=[CH:34][C:30]=1[C:31]([OH:33])=[O:32]

参加物

6

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 218864351,4-Dioxane--water (1/1)HCID 467397043-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 118043383tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate

生成物 1

HCID 118036162methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid収率 96%

試薬・触媒・溶媒 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒

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 (100 mg, 0.25 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (82 mg, 0.29 mmol), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (9 mg, 0.01 mmol) and potassium phosphate (157 mg, 0.74 mmol) in 1,4-dioxane/water (2.5 mL/0.25 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 methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid (114 mg, 96%). MS (ES+) C26H30N4O5 requires: 478, found: 479 [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-1391f68d032143e08655acb2a36661e3
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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