Sodium Carbonate → 1-(4-(6-(2-Amino-5-vinylnicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one

HRID 1929363Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1929363
[NH2:1][C:2]1[N:29]=[CH:28][C:27](Br)=[CH:26][C:3]=1[C:4]([C:6]1[N:11]=[C:10]([N:12]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:25])[CH2:20][C:21]([F:24])([F:23])[F:22])[CH2:14][CH2:13]2)[CH:9]=[CH:8][CH:7]=1)=[O:5].[CH:31](B1OC(C)(C)C(C)(C)O1)=[CH2:32].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:29]=[CH:28][C:27]([CH:31]=[CH2:32])=[CH:26][C:3]=1[C:4]([C:6]1[N:11]=[C:10]([N:12]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:25])[CH2:20][C:21]([F:24])([F:23])[F:22])[CH2:14][CH2:13]2)[CH:9]=[CH:8][CH:7]=1)=[O:5]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 249928341-(4-(6-(2-Amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one

Produkt 1

HCID 576907361-(4-(6-(2-Amino-5-vinylnicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-oneAusbeute 21,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of 1-(4-(6-(2-amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepan-1-yl)-3,3,3-trifluoropropan-1-one (355 mg, 0.73 mmol), vinyl boronic acid pinacol ester (0.15 ml, 0.88 mmol), tetrakis(triphenylphosphine)palladium(0) (42 mg) and a 2M aqueous solution of sodium carbonate (2 ml) in ethanol (1 ml) and toluene (3 ml) was heated under microwave irradiation at 110° C. for 5 hours. The reaction mixture was concentrated in vacuo. The residue was slurried in ethyl acetate, filtered to remove the inorganic salts and concentrated to dryness in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as an orange solid (68 mg, 21% yield).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. filtrationfiltered
  3. customto remove the inorganic salts
  4. concentrationconcentrated to dryness in vacuo
  5. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  6. customThe fractions were collected
  7. customfreeze-dried

Quellen und Nachweise

ORD-Eintrag
ord-1b970086f3e54c0d9ebd336d8f6cc308
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188071B2

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