3-Chloro-6-methylpyridazine → HCID 57431659, compound

HRID 545533Notes

Reaction equation

HRID 545533 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][CH:36]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][CH:15]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[C:10](B1OC(C)(C)C(C)(C)O1)[CH:11]=2.Cl[C:38]1[N:39]=[N:40][C:41]([CH3:44])=[CH:42][CH:43]=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][CH:36]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][CH:15]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[C:10]([C:38]1[N:39]=[N:40][C:41]([CH3:44])=[CH:42][CH:43]=1)[CH:11]=2

Participants

7

Reactant 2

HCID 2272543-Chloro-6-methylpyridazineHCID 59161262HCID 59161262, compound

Product 1

HCID 57431659HCID 57431659, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Dissolve N-[9-(3-flourobenzyl)-6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]isobutyramide (Preparation 23) (150 mg, 0.31 mmol) and 3-chloro-6-methylpyridazine (39 mg, 0.31 mmol) in dioxane (2.5 mL) and 2M Na2CO3 (388 μL). Sparge the solution with nitrogen for 5 min, add dichlorobis(triphenylphosphine)palladium (II) (11 mg, 0.016 mmol) and seal the reaction vessel. Heat to 140° C. in a microwave reactor for 30 min, then dilute with water (20 mL). Extract into EtOAc (3×25 mL), dry organics (MgSO4), filter, and concentrate in-vacuo to give the crude product (179 mg) as a brown solid. Purify the crude product on silica gel (12 g), eluting with 25-70% (4% (2M NH3/MeOH)/CH2Cl2)/hexanes to afford 35 mg (25%) of the title compound as a white solid. MS (ES): m/z 457 (M+1), 455 (M−1); HPLC (Method B) Rt=3.37 min (100%).

Workup

  1. customSparge the solution with nitrogen for 5 min
  2. customseal the reaction vessel
  3. extractionExtract into EtOAc (3×25 mL), dry organics (MgSO4)
  4. filtrationfilter
  5. concentrationconcentrate in-vacuo
  6. customto give the crude product (179 mg) as a brown solid
  7. customPurify the crude product on silica gel (12 g)
  8. washeluting with 25-70% (4% (2M NH3/MeOH)/CH2Cl2)/hexanes

Sources & evidence

ORD record
ord-4476077d2b54449da5031f40eba2efd3
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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