N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687463, compound

HRID 1473415Notes

Reaction equation

HRID 1473415 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+].[CH3:26][O:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][C:29]=1[C:38]1[C:47]2[C:42](=[CH:43][C:44]([S:48](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:50])=[O:49])=[CH:45][CH:46]=2)[N:41]=[CH:40][C:39]=1[N+:63]([O-:65])=[O:64]>C1COCC1.[Cl-].[NH4+].O>[CH3:26][O:27][C:28]1[CH:33]=[C:32]([C:34]([F:36])([F:35])[F:37])[CH:31]=[CH:30][C:29]=1[C:38]1[C:47]2[C:42](=[CH:43][C:44]([S:48]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=3)[C:9]3[S:10][CH:11]=[CH:12][N:13]=3)(=[O:50])=[O:49])=[CH:45][CH:46]=2)[N:41]=[CH:40][C:39]=1[N+:63]([O-:65])=[O:64]

Participants

7

Reactant 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687464HCID 86687464, compound

Product 1

HCID 86687463HCID 86687463, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (0.353 g, 1.603 mmol) and THF (7.29 ml) to give an opaque solution. The flask was cooled in a dry ice-acetone bath for 5 min to give a milky suspension, then lithium bis(trimethylsilyl)amide (1M in THF) (1.603 ml, 1.603 mmol) was added. The flask was removed from the bath for 5 min to give a clear solution, then resubmerged. The mixture appeared to remain a solution. After 5 min, a solution of perfluorophenyl 4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-nitroquinoline-7-sulfonate (1.125 g, 1.457 mmol) in THF (3 mL with a 2 mL wash) was added drop wise. The mixture was stirred for 45 min, then diluted with saturated aq ammonium chloride solution and warmed to room temperature. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g column, 0 to 40% EtOAc/Heptane) to give 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-nitro-N-(thiazol-2-yl)quinoline-7-sulfonamide (0.759 g, 1.204 mmol, 83% yield) as a yellow foam. m/z (ESI) 631.2 (M+H)+.

Workup

  1. customto give an opaque solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customto give a milky suspension
  4. customThe flask was removed from the bath for 5 min
  5. customto give a clear solution
  6. additionwas added drop wise
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (40-g column, 0 to 40% EtOAc/Heptane)

Sources & evidence

ORD record
ord-31b9d4eb20d54082a323c0d93393fef0
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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