2-Aminothiazole → 5-(2-chloro-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide

HRID 1473335Notes

Reaction equation

HRID 1473335 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16]([S:22](OC1C(F)=C(F)C(F)=C(F)C=1F)(=[O:24])=[O:23])=[CH:17]2.[S:37]1[CH:41]=[CH:40][N:39]=[C:38]1[NH2:42].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16]([S:22]([NH:42][C:38]1[S:37][CH:41]=[CH:40][N:39]=1)(=[O:24])=[O:23])=[CH:17]2

Participants

5

Reactant 3

HCID 21552-AminothiazoleHCID 2733832Lithium HexamethyldisilazideHCID 86687371Perfluorophenyl 5-(2-chloro-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonate

Product 1

HCID 866873895-(2-chloro-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamideYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a vial charged with perfluorophenyl 5-(2-chloro-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonate (0.200 g, 0.362 mmol) and THF (1 mL), was added thiazol-2-amine (0.040 g, 0.398 mmol) as a solution in THF (2 mL). The solution was cooled to −78° C., and a THF solution of lithium bis(trimethylsilyl)amide (0.724 ml, 0.724 mmol, 1M) was added dropwise by syringe. The solution was maintained at −78° C. for 5 min and then allowed to warm to rt. The solution was concentrated and the crude residue was absorbed onto a 5 g plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 5% to 90% EtOAc in hexane, to provide 5-(2-chloro-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide (0.112 g, 0.239 mmol) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 6.83 (d, J=4.59 Hz, 1H) 7.24 (d, J=4.59 Hz, 1H) 7.47 (d, J=8.98 Hz, 1H) 7.60 (d, J=7.16 Hz, 1H) 7.66-7.83 (m, 3H) 7.88 (d, J=8.23 Hz, 1H) 8.09 (s, 1H) 8.29 (d, J=8.33 Hz, 1H) 8.56 (d, J=1.71 Hz, 1H) 12.80 (br. s., 1H); m/z (ESI, +ve ion) 468.9 (M+H)+.

Workup

  1. temperatureThe solution was maintained at −78° C. for 5 min
  2. temperatureto warm to rt
  3. concentrationThe solution was concentrated
  4. customthe crude residue was absorbed onto a 5 g plug of silica gel
  5. custompurified by chromatography through a silica gel column (40 g)
  6. washeluting with a gradient of 5% to 90% EtOAc in hexane

Sources & evidence

ORD record
ord-7a51bc68de7c42fc93e23d3b08965b6d
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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