Diisopropylamine → 9-Cyclopropyl-6-fluoro-7-(2-(pyridin-2-YL)ethynyl)isothiazolo[5,4-B]quinoline-3,4(2H,9H)-dione

HRID 1640962Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1640962
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[C:7]3[C:17](=[O:18])[NH:16][S:15][C:8]=3[N:9]2[CH:12]2[CH2:14][CH2:13]2)=[CH:4][C:3]=1[F:20].[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)#[CH:22].C(NC(C)C)(C)C>CN(C=O)C.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>[CH:12]1([N:9]2[C:10]3[C:5](=[CH:4][C:3]([F:20])=[C:2]([C:22]#[C:21][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[CH:11]=3)[C:6](=[O:19])[C:7]3[C:17](=[O:18])[NH:16][S:15][C:8]2=3)[CH2:14][CH2:13]1

Komponenten

6

Edukt 3

HCID 7912DiisopropylamineHCID 137268EthynylpyridineHCID 599995297-Bromo-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-B]quinoline-3,4-dione

Produkt 1

HCID 599995409-Cyclopropyl-6-fluoro-7-(2-(pyridin-2-YL)ethynyl)isothiazolo[5,4-B]quinoline-3,4(2H,9H)-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Pd (PPh3)4 (4.5 mg) is added to a stirred solution of 7-bromo-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione (23 mg, 0.065 mmole) in DMF (1 mL), followed by the addition of 2-ethynylpyridine (2 equivalents, 0.13 mmole) and diisopropyl amine (0.15 mL.) under argon at room temperature. The reaction tube is sealed and then stirred in a microwave (100 W, 90° C.) until complete as monitored by LC/MS. The reaction mixture is filtered and the filtrate concentrated in vacuo. The residue is dissolved in a mixture of DMF: CHCl3: MeOH (1:8:1) and precipitated by adding diethyl ether (1-2 ml). This process is repeated three to five times. The resulting solid, 9-cyclopropyl-6-fluoro-7-(2-(pyridin-2-yl)ethynyl) isothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione, is washed with water to remove salt. The product is dried and analyzed. HPLC may be needed to obtain adequately pure product.

Aufarbeitung

  1. customThe reaction tube is sealed
  2. filtrationThe reaction mixture is filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. dissolutionThe residue is dissolved in a mixture of DMF: CHCl3: MeOH (1:8:1)
  5. customprecipitated
  6. additionby adding diethyl ether (1-2 ml)
  7. washThe resulting solid, 9-cyclopropyl-6-fluoro-7-(2-(pyridin-2-yl)ethynyl) isothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione, is washed with water
  8. customto remove salt
  9. customThe product is dried
  10. customto obtain adequately pure product

Quellen und Nachweise

ORD-Eintrag
ord-013897ccd0e64d0e97ae90be98156117
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08114888B2

Notizen zur Reaktion

Wird geladen…