o-Toluenesulfonyl chloride → HCID 90067166, compound

HRID 929229Notes

Reaction equation

HRID 929229 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C:29](=[N:32]O)[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.C1(C)C(S(Cl)(=O)=[O:41])=CC=CC=1>N1C=CC=CC=1.CO>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@H:24]3[C@H:25]4[O:31][CH2:30][C:29](=[O:41])[NH:32][C@H:26]4[O:27][CH2:28]3)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 2

HCID 8623o-Toluenesulfonyl chloride2×HCID 131735102HCID 131735102, compound

Product 1

HCID 90067166HCID 90067166, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

(3R,3aS,6aR)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,6a-tetrahydrofuro[3,2-b]furan-6-one oxime (20 mg, 0.043 mmol) was dissolved in pyridine and was cooled in an ice bath. Toluene sulfonyl chloride (21.2 mg, 0.11 mmol) was added in one portion and the mixture was stirred in an ice bath for 1 hour. The mixture was warmed to room temperature and additional toluene sulfonyl chloride (17 mg, 0.09 mmol) was added. After 2 hours, the solution was placed in a 60 degree oil bath for 1.5 hours and then cooled to room temperature. The reaction mixture was evaporated to give a foam, which was dissolved in methanol (2 mL) and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water to give the title compound. LC-MS: calculated for C24H19ClN4O4 462.11 observed m/e: 463.95 (M+14)+ (Rt 1.25/2 min); 1H NMR δ (ppm) (CD3OD): 7.93 (s, 1H), 7.78 and 7.73 (ABq, 4H), 7.70 (d, 2H), 7.48 (dd, 2H), 7.38 (dd, 1H), 6.44 (d, 1H), 5.48 (t, 1H), 4.83 (t, 1H), 4.63 (ABq, 2H), 4.50 (dd, 2H) and 4.45 (dd, 1H).

Workup

  1. temperaturewas cooled in an ice bath
  2. waitAfter 2 hours
  3. customwas placed in a 60 degree
  4. customfor 1.5 hours
  5. temperaturecooled to room temperature
  6. customThe reaction mixture was evaporated
  7. customto give a foam, which
  8. custompurified by preparative HPLC reverse phase (C-18)
  9. washeluting with a 20%-80% acetonitrile/water

Sources & evidence

ORD record
ord-693b4c9cf0454055ba09d068aa4a5f7d
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…