N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687723, compound

HRID 1473650Notes

Reaction equation

HRID 1473650 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([O:59][CH3:60])=[C:31]([C:33]2[C:42]3[C:37](=[CH:38][C:39]([S:43](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:45])=[O:44])=[CH:40][CH:41]=3)[C:36](=[O:58])[NH:35][N:34]=2)[CH:32]=1>C1COCC1>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([O:59][CH3:60])=[C:31]([C:33]2[C:42]3[C:37](=[CH:38][C:39]([S:43]([N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=4)[C:9]4[S:10][CH:11]=[CH:12][N:13]=4)(=[O:45])=[O:44])=[CH:40][CH:41]=3)[C:36](=[O:58])[NH:35][N:34]=2)[CH:32]=1

Participants

5

Reactant 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687720HCID 86687720, compound

Product 1

HCID 86687723HCID 86687723, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (63.5 mg, 0.288 mmol) and THF (1.60 mL) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 5 min to give a suspension. Lithium bis(trimethylsilyl)amide (1M in THF, 961 μl, 0.961 mmol) was added drop wise to give a light yellow solution. The mixture was stirred for 15 min. Then, a solution of perfluorophenyl 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (128 mg, 0.240 mmol) in THF (1.60 mL)) was added drop wise. LCMS after 1 h showed a complete conversion of SM to mainly product. The reaction was quenched with saturated aqueous ammonium chloride (0.5 mL) at −78° C. and then warmed to rt. The product was extracted with EtOAc. The organic layers was dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 20-50% EtOAc/heptanes) to give 1-(5-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-4-oxo-N-(thiazol-2-yl)-3,4-dihydrophthalazine-6-sulfonamide (56 mg, 41.0% yield) as an off-white solid. m/z (ESI) 569.0 (M+H)+.

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customto give a suspension
  4. customto give a light yellow solution
  5. waitLCMS after 1 h showed
  6. customThe reaction was quenched with saturated aqueous ammonium chloride (0.5 mL) at −78° C.
  7. extractionThe product was extracted with EtOAc
  8. dry with materialThe organic layers was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 20-50% EtOAc/heptanes)

Sources & evidence

ORD record
ord-070066069a504e2d96b88c0e94f01caa
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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