Hydrochloric Acid → 2-(Thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-7-amine

HRID 389552Notes

Reaction equation

HRID 389552 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:10]=[CH:11][CH:12]=[C:13]2[CH:17]=[C:16](B(O)O)[O:15][C:14]=12)=O)(C)(C)C.Br[C:29]1[C:37]2[C:32](=[CH:33][N:34]=[N:35][CH:36]=2)[S:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1.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.O>[S:31]1[C:32]2=[CH:33][N:34]=[N:35][CH:36]=[C:37]2[C:29]([C:16]2[O:15][C:14]3=[C:9]([NH2:8])[N:10]=[CH:11][CH:12]=[C:13]3[CH:17]=2)=[CH:30]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 228926363-Bromothieno[2,3-d]pyridazineHCID 66761297{7-[Bis(tert-butoxycarbonyl)amino]furo[2,3-c]pyridin-2-yl}boronic acid

Product 1

HCID 667606692-(Thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-7-amineYield 31.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
70 °C

Procedure

A suspension of {7-[bis(tert-butoxycarbonyl)amino]furo[2,3-c]pyridin-2-yl}boronic acid (200.0 mg, 0.5288 mmol), 3-bromothieno[2,3-d]pyridazine (77.1 mg, 0.358 mmol), Pd(PPh3)4 (21.8 mg, 0.0189 mmol), and potassium carbonate (150.5 mg, 1.089 mmol) in a 4:1 mixture of 1,4-dioxane to water (3.5 mL) was heated conventionally to 70° C. for 2.5 h. To the stirring reaction at 70° C., 4.0 M hydrochloric acid in 1,4-dioxane (2.0 mL) was added and was stirred for 1 h. The reaction mixture was cooled to ambient temperature, poured into saturated aqueous sodium bicarbonate, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by ISCO chromatography (3 to 15% methanol:dichloromethane) afforded 30.6 mg (31%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMF-d7): δ 10.43 (d, J=1.52 Hz, 1H), 10.10 (d, J=1.52 Hz, 1H), 8.92 (s, 1H), 7.83 (d, J=5.31 Hz, 1H), 7.67 (s, 1H), 6.95 (d, J=5.31 Hz, 1H), 6.66 (br s, 2H); MS (ESI): 269.13 [M+H]+; HPLC tR=2.16 min.

Workup

  1. customTo the stirring reaction at 70° C.
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. extractionextracted with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by ISCO chromatography (3 to 15% methanol:dichloromethane)

Sources & evidence

ORD record
ord-cd39c6b953274cb6a9a4e637b45cc908
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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