Potassium Carbonate → HCID 11704858, compound

HRID 2422014Notes

Reaction equation

HRID 2422014 reaction equation
C([N:5]1[C:9](=[O:10])[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:6]1(=[O:29])=[O:28])(C)(C)C.Br[CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][O:33]1.C([O-])([O-])=O.[K+].[K+]>C(O)(C(F)(F)F)=O>[C:22]1([C:7]2[S:6](=[O:29])(=[O:28])[N:5]([CH2:31][CH:32]3[CH2:36][CH2:35][CH2:34][O:33]3)[C:9](=[O:10])[C:8]=2[NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 14501Furan, 2-(bromomethyl)tetrahydro-HCID 114952832-tert-Butyl-5-phenyl-4-[(4-phenylbutyl)amino]isothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 11704858HCID 11704858, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
120 °C

Procedure

2-tert-Butyl-5-phenyl-4-[(4-phenylbutyl)amino]isothiazol-3(2H)-one 1,1-dioxide (Example 1) (0.1-50 g, 0.364 mmol) was dissolved in TFA (3 mL) and heated in a microwave reactor at 120° C. for 20 mins. TFA was removed in vacuo and coevaporated with DCM two times. The residue was dissolved in MeCN (3 mL) and mixed with 2-(bromomethyl)tetrahydrofuran (0.312 g, 1.892 mmol), TEA (0.148 g, 1.454 mmol) and K2CO3 (0.251 g, 1.818 mmol) and heated in a microwave reactor at 140° C. for 15 mins and at 160° C. for 80 mins. The residue was purified by column chromatography (Horizons Biotage) using a 75:25 mixture of hexane and EtOAc as eluant, to give the title compound (0.055 g, 36%); 1H NMR (500 Mz, CDCl3): δ 7.53-7.49 (m, 2H), 7.46-7.41 (m, 3H), 7.31-7.25 (m 2H), 7.22-7.18 (m, 1H), 7.10-7.06 (m, 22H), 5.30-5.24 (br m, 1H), 4.42-4.36 (m, 1H), 4.00-3.95 (m 1H), 3.86-3.79 (m 2H), 3.72-3.65 (dd 1H), 2.91-2.83 (m 2H), 2.49-2.43 (m 2H), 2.14-2.06 (m 1H), 2.06-1.89 (dm 2H), 1.77-1.68 (m 1H), 1.44-1.36 (m 4H); 13C NMR (125 MHz, CDCl3): δ 159.7, 141.7, 135.6, 131.9, 129.9, 128.8, 128.6, 128.5, 126.2, 125.1, 107.0, 68.5, 44.2, 35.4, 29.6, 29.2, 28.3, 25.7; Mass Spectrum: M−H+ 425.

Workup

  1. customTFA was removed in vacuo
  2. dissolutionThe residue was dissolved in MeCN (3 mL)
  3. temperatureheated in a microwave reactor at 140° C. for 15 mins and at 160° C. for 80 mins
  4. customThe residue was purified by column chromatography (Horizons Biotage)
  5. additiona 75:25 mixture of hexane and EtOAc as eluant

Sources & evidence

ORD record
ord-aa5a4025f5ab4d9fa0a49c1c9e8cc010
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

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