Dimethylformamide → [2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5,11-dihydro-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)-methanone

HRID 2288677

Reaktionsgleichung

Reaktionsgleichung von HRID 2288677
[N:1]1[C:6]2[NH:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[NH:10][CH2:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[Br:22][C:23]1[CH:31]=[C:30](F)[CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26].C[N:34]([CH3:37])C=O>O.ClCCl>[Br:22][C:23]1[CH:31]=[C:30]([N:34]2[CH:37]=[CH:9][C:8]([CH3:15])=[N:7]2)[CH:29]=[CH:28][C:24]=1[C:25]([N:10]1[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[NH:7][C:6]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:11]1)=[O:26]

Komponenten

7

Edukt 4

HCID 6228Dimethylformamide2×HCID 11430Potassium CarbonateHCID 27833462-Bromo-4-fluorobenzoyl chlorideHCID 110307606,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

Produkt 1

HCID 9868852[2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5,11-dihydro-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)-methanoneAusbeute 59,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine of Example 1, Step B (5.15 g, 26.1 mmol) in dimethylformamide (70 mL) under nitrogen was added potassium carbonate (7.95 g, 57.51 mmol). The mixture was cooled and treated dropwise with a solution of crude 2-bromo-4-fluorobenzoyl chloride of Step A (31.37 mmol) in dimethylformamide (30 mL). After stirring at room temperature for 75 minutes the mixture was diluted with water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate and evaporated to dryness to give a brown solid foam. The crude material was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with a hexane-ethyl acetate gradient (from 95:5 to 75:25) provided the pure title compound (6.18 g, 59.5%) along with some impure material (1.2 g). The pure material was triturated with hexane to provide an off-white solid foam, which was used as such in the next step.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic extracts were dried over magnesium sulfate
  4. customevaporated to dryness
  5. customto give a brown solid foam
  6. customabsorbed onto a silica Merck-60 flash column
  7. washElution with a hexane-ethyl acetate gradient (from 95:5 to 75:25)

Quellen und Nachweise

ORD-Eintrag
ord-60a6c813a0504514b9bd07eeb63b73c2
Quelldatensatz
uspto-grants-2000_07
Patentnummer
US06090803

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