Sulfamide → (3S,4R)-4-[3,5-bis(trifluoromethyl)phenyl]-2-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-3-methyl-1,2,5-thiadiazolidine 1,1-dioxide

HRID 1994514Notes

Reaction equation

HRID 1994514 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@@H:13]([NH2:39])[C@@H:14]([NH:16][CH2:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=2[C:28]2[CH:33]=[C:32]([CH:34]([CH3:36])[CH3:35])[CH:31]=[CH:30][C:29]=2[O:37][CH3:38])[CH3:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[S:42](N)(N)(=[O:44])=[O:43]>N1C=CC=CC=1>[F:1][C:2]([F:40])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]2[NH:39][S:42](=[O:44])(=[O:43])[N:16]([CH2:17][C:18]3[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][C:19]=3[C:28]3[CH:33]=[C:32]([CH:34]([CH3:35])[CH3:36])[CH:31]=[CH:30][C:29]=3[O:37][CH3:38])[C@H:14]2[CH3:15])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

4

Reactant 2

HCID 82267SulfamideHCID 59135060(1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-N2-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}propane-1,2-diamine

Product 1

HCID 11700257(3S,4R)-4-[3,5-bis(trifluoromethyl)phenyl]-2-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-3-methyl-1,2,5-thiadiazolidine 1,1-dioxide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
120 °C

Procedure

A glass reaction tube was charged with (1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-N2-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}propane-1,2-diamine (15.9 mg, 0.0269 mmol), sulfamide (4 mg, 0.0403 mmol), and pyridine (600 μL). The tube was flushed with N2, sealed, and heated at 120° C. for 2 h. The reaction was then cooled to room temperature, diluted with EtOAc (40 mL) and washed with H2O, 1N HCl, and brine (10 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 25% EtOAc/hexanes afforded (3S,4R)-4-[3,5-bis(trifluoromethyl)phenyl]-2-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-3-methyl-1,2,5-thiadiazolidine 1,1-dioxide. Rf=0.27 (25% EtOAc/hexanes). LCMS=655.2 (M+1)+. 1H NMR (C6D6, 500 MHz; atropisomers present) δ 6.51-8.19 (m, 9H), 3.64-4.53 (m, 4H), 3.00-3.18 (m, 4H), 2.73 (m, 1H), 1.13-1.20 (m, 6H), −0.03-0.09 (m, 3H).

Workup

  1. customA glass reaction tube
  2. customThe tube was flushed with N2
  3. customsealed
  4. temperatureThe reaction was then cooled to room temperature
  5. additiondiluted with EtOAc (40 mL)
  6. washwashed with H2O, 1N HCl, and brine (10 mL each)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the residue by flash chromatography with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-6fdc2325805a43d3be7b21ce4f0d811c
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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