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

HRID 56364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 56364
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]

Komponenten

6

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1391f68d032143e08655acb2a36661e3
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434700B2

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