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

HRID 1640962Notes

Reaction equation

HRID 1640962 reaction equation
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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-013897ccd0e64d0e97ae90be98156117
Source dataset
uspto-grants-2012_02
Patent number
US08114888B2

Reaction notes

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