Water → N-ethoxy-1-methyl-2,2-dioxo-6-[1-(3-pyridyl)pyrazol-4-yl]pyrido[3,2-c]thiazin-4-imine

HRID 1478537Notes

Reaction equation

HRID 1478537 reaction equation
C([O-])([O-])=O.[Na+].[Na+].O.CC1(C)C(C)(C)OB([C:16]2[CH:17]=[N:18][N:19]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[CH:20]=2)O1.Br[C:29]1[CH:30]=[CH:31][C:32]2[N:33]([CH3:45])[S:34](=[O:44])(=[O:43])[CH2:35][C:36](=[N:39][O:40][CH2:41][CH3:42])[C:37]=2[N:38]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[CH2:41]([O:40][N:39]=[C:36]1[CH2:35][S:34](=[O:44])(=[O:43])[N:33]([CH3:45])[C:32]2[CH:31]=[CH:30][C:29]([C:16]3[CH:17]=[N:18][N:19]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:20]=3)=[N:38][C:37]1=2)[CH3:42]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 574162183-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridineHCID 1236954456-bromo-N-ethoxy-1-methyl-2,2-dioxo-pyrido[3,2-c]thiazin-4-imine

Product 1

HCID 123930255N-ethoxy-1-methyl-2,2-dioxo-6-[1-(3-pyridyl)pyrazol-4-yl]pyrido[3,2-c]thiazin-4-imine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To Na2CO3 (183 mg, 1.71 mmol) was added water (1.5 ml) and acetonitrile (2 ml) and the solution was degassed for 5 min with argon. 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]pyridine (111 mg, 0.41 mmol), 6-bromo-N-ethoxy-1-methyl-2,2-dioxo-pyrido[3,2-c]thiazin-4-imine (114 mg, 0.34 mmol) and Pd(dppf)Cl2 (25 mg, 0.034 mmol) were added sequentially followed by rinsing the flask with acetonitrile (2 ml). The mixture was stirred at 80° C. for 1.5 h followed by cooling to ambient temperature. Water and ethyl acetate were added then the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography eluting with ethyl acetate/heptane, gradient, afforded N-ethoxy-1-methyl-2,2-dioxo-6-[1-(3-pyridyl)pyrazol-4-yl]pyrido[3,2-c]thiazin-4-imine as a red solid as a single isomer.

Workup

  1. customthe solution was degassed for 5 min with argon
  2. washby rinsing the flask with acetonitrile (2 ml)
  3. temperatureby cooling to ambient temperature
  4. additionWater and ethyl acetate were added
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with ethyl acetate
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography
  11. washeluting with ethyl acetate/heptane, gradient

Sources & evidence

ORD record
ord-48b134bcfaec4092be4d52809c10b904
Source dataset
uspto-grants-2016_08
Patent number
US09403845B2

Reaction notes

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