Acetic Acid → HCID 86687530, compound

HRID 1473480Notes

Reaction equation

HRID 1473480 reaction equation
COC1C=CC(C[NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=CC=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](Cl)(=[O:50])=[O:49])=[CH:45][CH:46]=2)[N:41]=[N:40][CH:39]=1.C(O)(=O)C>C1COCC1.CO.O>[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]([NH:8][C:9]3[S:10][CH:11]=[CH:12][N:13]=3)(=[O:50])=[O:49])=[CH:45][CH:46]=2)[N:41]=[N:40][CH:39]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687531HCID 86687531, compound

Product 1

HCID 86687530HCID 86687530, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22242641Methanol--water (1/1)Solvent

Procedure

To a flask containing an ice cold suspension of N-(4-methoxybenzyl)thiazol-2-amine (40.2 mg, 0.182 mmol) in THF (668 μl) was added lithium bis(trimethylsilyl)amide (1M in THF) (191 μl, 0.191 mmol) drop wise over 10 min. The mixture was stirred for 15 min prior to the drop wise addition of a solution of 4-(2-methoxy-4-(trifluoromethyl)phenyl)cinnoline-7-sulfonyl chloride (70 mg, 0.174 mmol) in THF (0.7 ml). The solution was allowed to stir for 1 hr (ice melt) providing a brown solution. To the mixture was added acetic acid (about 100 μl) and the mixture dried under reduced pressure. To the crude material was added DCM (1 ml) followed by TFA (0.3 ml) and the mixture stirred at room temperature for 2 hrs. The mixture was dried under reduced pressure and the crude material purified with a 25 g spherical silica column (15 μm spherical, Interchim) ramping EtOAc in heptane (0 to 70%, 10% DCM isocratic throughout) providing product which was lyophilized from MeOH/H2O to afford 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)cinnoline-7-sulfonamide (34 mg, 0.073 mmol, 41.9% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) μ ppm 3.79 (s, 3H) 6.91 (d, J=4.50 Hz, 1H) 7.32 (d, J=4.60 Hz, 1H) 7.51-7.60 (m, 2H) 7.66 (d, J=7.53 Hz, 1H) 7.77-7.84 (m, 1H) 8.08 (dd, J=8.90, 1.86 Hz, 1H) 8.87 (dd, J=1.81, 0.54 Hz, 1H) 9.45 (s, 1H) 13.03 (br. s., 1H). m/z (ESI) 467.2 (M+H)+.

Workup

  1. additionTo a flask containing
  2. stirringto stir for 1 hr (ice melt)
  3. customproviding a brown solution
  4. customthe mixture dried under reduced pressure
  5. additionTo the crude material was added DCM (1 ml)
  6. stirringthe mixture stirred at room temperature for 2 hrs
  7. customThe mixture was dried under reduced pressure
  8. customthe crude material purified with a 25 g spherical silica column (15 μm spherical, Interchim)
  9. customproviding product which

Sources & evidence

ORD record
ord-42181229aa5544b290f079d2a1c0b144
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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