Methanol → HCID 86661323, compound

HRID 1685092Notes

Reaction equation

HRID 1685092 reaction equation
N#N.[F:3][C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][CH:33]=1)[CH2:7][NH:8][C:9]([NH:11][C:12]1[S:13][CH:14]=[C:15]([CH2:17][N:18]([CH3:30])[C:19]([C:21]2[CH:26]=[C:25]([O:27][CH3:28])[N:24]=[N:23][C:22]=2Cl)=[O:20])[N:16]=1)=[O:10].[CH3:34][Al](C)C.CO>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>[F:3][C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][CH:33]=1)[CH2:7][NH:8][C:9](=[O:10])[NH:11][C:12]1[S:13][CH:14]=[C:15]([CH2:17][N:18]([CH3:30])[C:19]([C:21]2[CH:26]=[C:25]([O:27][CH3:28])[N:24]=[N:23][C:22]=2[CH3:34])=[O:20])[N:16]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 947NitrogenHCID 16682925TrimethylaluminumHCID 86661317HCID 86661317, compound

Product 1

HCID 86661323HCID 86661323, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

N2 was bubbled for 15 minutes through a solution of 1-(3-fluorobenzyl)-3-(4-((3-chloro-6-methoxy-N-methylpyridazine-4-carboxamido)methyl)-thiazol-2-yl)urea (118 mg, 0.25 mmol) in 1,4-dioxane. Pd(PPh3)4 (15 mg, 13 μmol) was added followed by AlMe3 (250 μl, 2 M in toluene, 0.51 mmol). The mixture was refluxed for 4 hours and MeOH was added. Silica (300 mg) was added and the volatiles were removed in vacuo. The residue was brought on a column and purified by chromatography (CH2Cl2+5% 7N NH3 in MeOH) to afford the title product (60 mg, 0.13 mmol) as an off-white solid in 52% yield.

Workup

  1. temperatureThe mixture was refluxed for 4 hours
  2. additionSilica (300 mg) was added
  3. customthe volatiles were removed in vacuo
  4. custompurified by chromatography (CH2Cl2+5% 7N NH3 in MeOH)

Sources & evidence

ORD record
ord-804913a31f2b4e639751570b8ca10863
Source dataset
uspto-grants-2012_04
Patent number
US08148380B2

Reaction notes

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