2-Aminothiazole → HCID 71586127, compound

HRID 1473309Notes

Reaction equation

HRID 1473309 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:17][N:18]1[C:22]([C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=2[C:33]2[CH:42]=[CH:41][CH:40]=[C:39]3[C:34]=2[CH:35]=[CH:36][C:37]([S:43](Cl)(=[O:45])=[O:44])=[CH:38]3)=[CH:21][CH:20]=[N:19]1.[NH4+].[Cl-]>C1COCC1>[CH3:17][N:18]1[C:22]([C:23]2[CH:28]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:26]=[CH:25][C:24]=2[C:33]2[CH:42]=[CH:41][CH:40]=[C:39]3[C:34]=2[CH:35]=[CH:36][C:37]([S:43]([NH:1][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)(=[O:45])=[O:44])=[CH:38]3)=[CH:21][CH:20]=[N:19]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 86687366HCID 86687366, compound

Product 1

HCID 71586127HCID 71586127, compoundYield 57.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A round bottom flask was charged with 2-aminothiazole (20.26 mg, 0.202 mmol) and sealed with septum. THF (1686 μl) was added and the solution was cooled to 0° C. A THF solution of lithium bis(trimethylsilyl)amide (253 μl, 0.253 mmol, 1 M) was added and the solution was maintained at 0° C. for 5 min To this solution was added 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonyl chloride (76.0 mg, 0.169 mmol) as a solution in THF (3 mL total). After 15 minutes at 0° C., saturated aqueous NH4Cl (1 mL) was added to the reaction mixture. The reaction mixture was partitioned between saturated aqueous NH4Cl (10 mL) and EtOAc (15 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic extracts were dried over Na2SO4 and concentrated under a vacuum. The residue was taken up in minimal DMSO and purified by preparative HPLC (column: Phenomenex C18 150×30 mm, 5 μm (Phenomenex, Torrance, Calif.): 20 to 90% CH3CN:H2O (1% TFA modifier) over 15 min). Fractions were combined and concentrated to afford 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide (50.0 mg, 0.097 mmol) as a white amorphous solid. 1H NMR (400 MHz, d6-acetone) δ ppm 3.50 (s, 3H) 5.84 (d, J=1.86 Hz, 1H) 6.74 (d, J=4.69 Hz, 1H) 7.02 (d, J=1.96 Hz, 1H) 7.19 (d, J=4.70 Hz, 1H) 7.46 (d, J=7.04 Hz, 1H) 7.51-7.59 (m, 1H) 7.64 (d, J=8.90 Hz, 1H) 7.72 (d, J=8.02 Hz, 1H) 7.75-7.82 (m, 1H) 7.87 (s, 1H) 7.94 (d, J=8.12 Hz, 1H) 8.05 (d, J=8.31 Hz, 1H) 8.44 (s, 1H); m/z (ESI, +ve ion) 515.2 (M+H)+.

Workup

  1. customsealed with septum
  2. temperaturethe solution was maintained at 0° C. for 5 min To this solution
  3. customThe reaction mixture was partitioned between saturated aqueous NH4Cl (10 mL) and EtOAc (15 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. concentrationconcentrated under a vacuum
  8. custompurified by preparative HPLC (column: Phenomenex C18 150×30 mm, 5 μm (Phenomenex, Torrance, Calif.): 20 to 90% CH3CN:H2O (1% TFA modifier) over 15 min)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-57ea637f43964de7bb81b5e2d5de1ab9
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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