2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → 2-Morpholino-4-(naphthalen-2-ylmethyl)thiazole-5-sulfonamide

HRID 2402136Notes

Reaction equation

HRID 2402136 reaction equation
Br[C:2]1[N:3]=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[S:5][C:6]=1[S:7]([NH2:10])(=[O:9])=[O:8].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[Br-].[CH:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=[CH:49][C:48]=1[CH2:57][Zn+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[O:14]1[CH2:15][CH2:16][N:11]([C:4]2[S:5][C:6]([S:7]([NH2:10])(=[O:9])=[O:8])=[C:2]([CH2:57][C:48]3[CH:49]=[CH:50][C:51]4[C:56](=[CH:55][CH:54]=[CH:53][CH:52]=4)[CH:47]=3)[N:3]=2)[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 667475964-Bromo-2-morpholinothiazole-5-sulfonamide2×HCID 178419770HCID 178419770, compound

Product 1

HCID 568328112-Morpholino-4-(naphthalen-2-ylmethyl)thiazole-5-sulfonamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a dried flask was added 4-bromo-2-morpholinothiazole-5-sulfonamide (194 mg, 0.591 mmol), THF (4.79 mL), palladium(II) acetate (1.33 mg, 0.00591 mmol) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.85 mg, 0.0118 mmol). The mixture was stirred for 5 minutes, and a 0.500 M solution of 2-napthylmethylzinc bromide in THF (4.14 mL, 2.04 mmol) was then added dropwise over 30 minutes. The reaction was stirred at room temperature for 1 hour and quenched with saturated ammonium chloride (10 mL). The reaction was extracted with ethyl acetate (2×25 mL) and the combined organic layers were washed with water (15 mL), dried and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60) which gave a mixture of the desired product with residual 4-bromo-2-morpholinothiazole-5-sulfonamide. This material was purified by preparative reverse phase chromatography to give 51 mg (22% yield) of the title compound as a white solid. LC/MS (FA) ES+ 390. 1H NMR (400 MHz, DMSO-d6) δ: 7.85-7.77 (m, 4H), 7.71 (bs, 2H), 7.50-7.42 (m, 3H), 4.25 (s, 2H), 3.64-3.61 (m, 4H), 3.35-3.32 (m, 4H).

Workup

  1. stirringThe reaction was stirred at room temperature for 1 hour
  2. customquenched with saturated ammonium chloride (10 mL)
  3. extractionThe reaction was extracted with ethyl acetate (2×25 mL)
  4. washthe combined organic layers were washed with water (15 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60) which
  8. customgave

Sources & evidence

ORD record
ord-5bf81109426d40afa7ccc8ad0b4c42d0
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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