N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687470, compound

HRID 1473420Notes

Reaction equation

HRID 1473420 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+].[Br:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[CH:30]=[N:29][CH:28]=1>C1COCC1>[Br:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37]([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:39])=[O:38])=[CH:34][CH:35]=2)[CH:30]=[N:29][CH:28]=1

Participants

5

Reactant 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium Hexamethyldisilazide2×HCID 86687467HCID 86687467, compound

Product 1

HCID 86687470HCID 86687470, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a flask charged with N-(4-methoxybenzyl)thiazol-2-amine (180 mg, 0.816 mmol) was added THF (3 ml) and the resulting mixture cooled in an ice water bath prior to the addition of lithium bis(trimethylsilyl)amide (1M in THF) (855 μl, 0.855 mmol). The resulting light brown solution was stirred for 15 min at 0° C. prior to the addition of a solution of perfluorophenyl 4-bromoisoquinoline-7-sulfonate (353 mg, 0.777 mmol) in THF (2 ml), followed by 1 ml THF wash. The resulting solution was allowed to stir and warm slowly to room temperature (ice melt). After 2 hr LC/MS indicated about 70% conversion fairly cleanly, with starting amine and PFP ester present (no change from 1 hr). The solution was cooled back to 0° C. and 0.5 eq LiHMDS (1 M) was added. After 1 hr LC/MS indicated complete consumption of starting material. To the mixture was added 400 μl acetic acid and the mixture was dried under reduced pressure and purified with a 40 g HP Silicycle column (SiliCycle, Inc. Quebec City, Canada) ramping EtOAc in heptane (0 to 50%, 10% DCM throughout) affording product as a white solid 4-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (Intermediate PPPP) (202 mg, 0.412 mmol, 53.0% yield). m/z (ESI) 490.0 (M+H)+.

Workup

  1. temperaturethe resulting mixture cooled in an ice water bath
  2. washwash
  3. stirringto stir
  4. temperaturewarm slowly to room temperature (ice melt)
  5. waitAfter 2 hr LC/MS indicated
  6. waitabout 70% conversion fairly cleanly, with starting amine and PFP ester present (no change from 1 hr)
  7. temperatureThe solution was cooled back to 0° C.
  8. waitAfter 1 hr LC/MS indicated complete
  9. customconsumption of starting material
  10. additionTo the mixture was added 400 μl acetic acid
  11. customthe mixture was dried under reduced pressure
  12. custompurified with a 40 g HP Silicycle column (SiliCycle, Inc. Quebec City, Canada)

Sources & evidence

ORD record
ord-6c78fbc94cdc47d8b548020cdec50330
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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