Sodium Hydroxide → HCID 59570822, compound

HRID 2068001Notes

Reaction equation

HRID 2068001 reaction equation
C[Al](C)C.[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH2:9][NH2:10].C([O:18][C:19](=O)[NH:20][C:21]1[S:22][C:23]([F:36])=[C:24]([CH2:26][S:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[N:25]=1)(C)(C)C.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH2:9][NH:10][C:19]([NH:20][C:21]1[S:22][C:23]([F:36])=[C:24]([CH2:26][S:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[N:25]=1)=[O:18]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 668533-FluorobenzylamineHCID 16682925TrimethylaluminumHCID 86647351HCID 86647351, compound

Product 1

HCID 59570822HCID 59570822, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of 2 M trimethylaluminum in toluene (0.68 mL, 1.4 mmol) was treated with 3-fluorobenzylamine (0.16 mL, 1.4 mmol), followed by a solution of [5-fluoro-4-(4-methoxy-phenylsulfanylmethyl)-thiazol-2-yl]-carbamic acid tert-butyl ester (250 mg, 0.68 mmol), obtained above, in anhydrous toluene (3 mL). The resulting solution was heated at 80-100° C. for 3 hours. The cooled reaction mixture was hydrolyzed by sequential addition of: water (50 uL); 15% aqueous sodium hydroxide (50 uL); and water (150 uL). After stifling overnight, the granular aluminum salts were removed by filtration. The filtrate was concentrated and purified by silica gel chromatography (EtOAc) to afford Intermediate 106: 1-(3-fluoro-benzyl)-3-[5-fluoro-4-(4-methoxy-phenylsulfanylmethyl)-thiazol-2-yl]-urea as a pale yellow solid (168 mg, 59% yield).

Workup

  1. customThe cooled reaction mixture
  2. customthe granular aluminum salts were removed by filtration
  3. concentrationThe filtrate was concentrated
  4. custompurified by silica gel chromatography (EtOAc)

Sources & evidence

ORD record
ord-02b90577780a4ded95240fafb69440f5
Source dataset
uspto-grants-2012_10
Patent number
US08293919B2

Reaction notes

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