Potassium Carbonate → methyl (4-{3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-4-vinyl-2-thienyl}pyridin-2-yl)carbamate

HRID 2401825Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2401825
Br[C:2]1[C:3]([C:29]#[N:30])=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25](=[O:28])[O:26][CH3:27])[CH:19]=2)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:8]=1.[CH:31]([B-](F)(F)F)=[CH2:32].[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.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>[C:29]([C:3]1[C:2]([CH:31]=[CH2:32])=[C:6]([C:7]2[N:11]=[CH:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:8]=2)[S:5][C:4]=1[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25](=[O:28])[O:26][CH3:27])[CH:19]=1)#[N:30]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 23679353Potassium vinyltrifluoroborateHCID 68095977Methyl (4-{4-bromo-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate

Produkt 1

HCID 68100370methyl (4-{3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-4-vinyl-2-thienyl}pyridin-2-yl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of methyl (4-{4-bromo-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate (1.14 g, 2.33 mmol), potassium vinyltrifluoroborate (0.624 g, 4.66 mmol), tetrakis(triphenylphosphine)platinum (0) (0.145 g, 0.116 mmol) and potassium carbonate (0.967 g, 7.00 mmol) in N,N-dimethylformamide (14.0 mL) and water (5.0 mL) in a microwave vial was heated under nitrogen atmosphere at 140° C. in a microwave for 15 min. The mixture was cooled to room temperature, quenched with water, extracted with DCM, washed with water then brine, dried over Na2SO4, filtered and rotavaped to give a crude product. Purification on a silica gel column using MeOH/DCM (0/100 to 5/95) afforded the desired product (1.16 g, with PPh3 and O═PPh3 contaminated) with Rf on TLC (MeOH/DCM 5/95) of 0.4, and de-carbamide product (0.627 g, yield 58%). LC/MS: (FA) ES+ 437. 1H NMR (400 MHz, d-chloroform) δ 8.52 (s, 1H), 8.45 (s, 1H), 8.41 (m, 1H), 8.33 (s, 1H), 7.51-7.59 (m, 1H), 7.46-7.49 (m, 1H), 6.28-6.33 (m, 1H), 5.66-5.69 (m, 1H), 5.51-5.54 (m, 1H), 4.09-4.12 (m, 1H), 3.86 (s, 3H), 3.75-3.78 (m, 1H), 2.00-2.20 (m, 3H), 1.68-1.77 (m, 3H).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. customquenched with water
  3. extractionextracted with DCM
  4. washwashed with water
  5. dry with materialbrine, dried over Na2SO4
  6. filtrationfiltered
  7. customto give a crude product
  8. customPurification on a silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-41de3af0f2ed4e0ab9bf2badc1619fc0
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796268B2

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