Sodium Bicarbonate → 9-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6-fluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione

HRID 1640956Notes

Reaction equation

HRID 1640956 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:26])[C:7]3[C:17](=[O:18])[N:16](C(OC(C)(C)C)=O)[S:15][C:8]=3[N:9]2[CH:12]2[CH2:14][CH2:13]2)=[CH:4][C:3]=1[F:27].C(OC([C:33]1[C:42](=O)[C:41]2[C:36](=[CH:37]C(Br)=C(F)C=2)[N:35](C2CC2)[C:34]=1SC)=O)C.[C:51]([O-])(O)=O.[Na+]>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.CN(C=O)C>[CH:12]1([N:9]2[C:10]3[C:5](=[CH:4][C:3]([F:27])=[C:2]([C:42]4[CH:33]=[C:34]([CH3:51])[N:35]=[C:36]([CH3:37])[CH:41]=4)[CH:11]=3)[C:6](=[O:26])[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 516892Sodium BicarbonateHCID 599995377-Bromo-1-cyclopropyl-6-fluoro-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl esterHCID 59999538Tert-butyl 7-bromo-9-cyclopropyl-6-fluoro-3,4-dioxoisothiazolo[5,4-B]quinoline-2(3H,4H,9H)-carboxylate

Product 1

HCID 116753319-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6-fluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 7-bromo-9-cyclopropyl-6-fluoro-3,4-dioxoisothiazolo[5,4-b]quinoline-2(3H,4H,9H)-carboxylate (8, 22 mg, 0.048 mmol), 4-(2,6-Dimethylpyridyl)boronic acid (5, 23 mg, 0.12 mmol) and Pd (PPh3)4 (4 mg) in a solution of DMF (1 ml) and 1M NaHCO3 (0.22 ml) is sealed in a microwave reaction vessel with a stirrer. After filling with helium, the mixture is microwaved at 100 W, 130° C. for 10 minutes. The reaction is followed by LC-MS. The reaction mixture is filtered and the filtrate evaporated to dryness. The residue is washed with a solution of methanol and ethyl ether (5:95) (3×3 ml), and dried in vacuum yielding pure product 25. 1H NMR (300 MHz, DMSO-d6) δ 1.1-1.3 (m, 4H, —CH2—), 1.53 (s, 1H, —CH—), 2.47 (s, 6H, —CH3), 7.27 (s, 2H, Ar), 7.93, (d, 1H, Ar), 8.2 (d, 1H, Ar). 19F NMR (350 MHz, DMSO-d6) δ 125 (s, 1F). MS, m/z 382 (M+1).

Workup

  1. customis sealed in a microwave reaction vessel with a stirrer
  2. customthe mixture is microwaved at 100 W, 130° C. for 10 minutes
  3. filtrationThe reaction mixture is filtered
  4. customthe filtrate evaporated to dryness
  5. washThe residue is washed with a solution of methanol and ethyl ether (5:95) (3×3 ml)
  6. customdried in vacuum

Sources & evidence

ORD record
ord-d8c02065d16d4adbbffd3cffb63be356
Source dataset
uspto-grants-2012_02
Patent number
US08114888B2

Reaction notes

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