Potassium Carbonate → HCID 44125255, compound

HRID 1162479Notes

Reaction equation

HRID 1162479 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]([NH:21][CH3:22])[CH3:20])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[CH:33][C:34]3[N:35]([CH:37]=[C:38]([NH:40][C:41](=[O:43])[CH3:42])[N:39]=3)[N:36]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(Cl)Cl.CO>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:31]2[CH:32]=[CH:33][C:34]3[N:35]([CH:37]=[C:38]([NH:40][C:41](=[O:43])[CH3:42])[N:39]=3)[N:36]=2)=[CH:3][C:4]=1[NH:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([CH:19]([NH:21][CH3:22])[CH3:20])=[CH:15][CH:14]=1)(=[O:12])=[O:11]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 57749440N-(6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide2×HCID 57749441HCID 57749441, compound

Product 1

HCID 44125255HCID 44125255, compoundYield 42%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

N-(5-bromo-2-chloropyridin-3-yl)-4-(1-(methylamino)ethyl)benzenesulfonamide (488 mg, 1.21 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (590.6 mg, 1.955 mmol), potassium carbonate (600 mg, 4.34 mmol), and Pd(dppf)Cl2*DCM complex (117.5 mg, 0.1439 mmol) were suspended in DME (8.0 mL) and water (2.0 mL). The reaction flask was fit with a reflux condensor and placed in a preheated oil bath (100 C) and stirred under nitrogen for 75 minutes. Then, the reaction was cooled to room temperature, and more N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (213 mg, 0.705 mmol) was added, and stirring was continued at 100 C. After another hour, the reaction was cooled to room temperature, diluted with DCM and MeOH, and filtered through a pad of Celite® (diatomaceous earth). The filtrate was concentrated and purified using silica gel on a filter (DCM to 50:1 to 20:1 to 5:1 to 3:1 DCM/2 N ammonia in MeOH). The fractions with product were collected, concentrated, treated with MeOH, and filtered. The solid was washed with MeOH, Et2O, DCM, MeOH, and Et2O. The solid was then collected and dried under high vacuum to afford N-(6-(6-chloro-5-(4-(1-(methylamino)ethyl)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (253 mg, 42% yield) as a brown, amorphous solid. MS (ESI positive ion) m/z: 500 (M+1). Calcd for C22H22ClN7O3S: 499. 1H NMR (400 MHz, DMSO-d6): δ ppm 10.93 (s, 1H), 8.25 (s, 1H), 8.12-8.06 (m, 2H), 8.03 (d, J=9.54 Hz, 1H), 7.85 (d, J=8.53 Hz, 2H), 7.56-7.47 (m, 4H), 4.32-4.20 (m, 1H), 2.40 (s, 3H), 2.11 (s, 3H), 1.48 (d, J=6.53 Hz, 3H).

Workup

  1. customplaced in a preheated oil bath
  2. stirringstirring
  3. waitAfter another hour
  4. temperaturethe reaction was cooled to room temperature
  5. filtrationfiltered through a pad of Celite® (diatomaceous earth)
  6. concentrationThe filtrate was concentrated
  7. custompurified
  8. filtrationa filter (DCM to 50:1 to 20:1 to 5:1 to 3:1 DCM/2 N ammonia in MeOH)
  9. customThe fractions with product were collected
  10. concentrationconcentrated
  11. additiontreated with MeOH
  12. filtrationfiltered
  13. washThe solid was washed with MeOH, Et2O, DCM, MeOH, and Et2O
  14. customThe solid was then collected
  15. customdried under high vacuum

Sources & evidence

ORD record
ord-06c834916eb64fa88d841e8d7688a169
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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