Toluene-p-sulphonic anhydride → HCID 178503007, compound

HRID 244153Notes

Reaction equation

HRID 244153 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:28]3[CH2:33][CH2:32][C@H:31]([CH2:34][OH:35])[CH2:30][CH2:29]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([C:15]([CH3:27])=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.[C:36]1([CH3:56])[CH:41]=[CH:40][C:39]([S:42]([O:45]S(C2C=CC(C)=CC=2)(=O)=O)(=[O:44])=[O:43])=[CH:38][CH:37]=1.[C:57](=O)(O)[O-].[Na+]>N1C=CC=CC=1>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:28]3[CH2:33][CH2:32][C@H:31]([CH2:34][OH:35])[CH2:30][CH2:29]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([C:15]([CH3:27])=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.[CH3:56][C:36]1[CH:41]=[CH:40][C:39]([S:42]([O:45][CH3:57])(=[O:44])=[O:43])=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 77773Toluene-p-sulphonic anhydrideHCID 516892Sodium BicarbonateHCID 178422623HCID 178422623, compound

Product 1

HCID 178503007HCID 178503007, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

trans-{4-[8-Amino-(4-methyl-2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]cyclohexyl}methanol (200 mg, 0.43 mmol) and toluene-4-sulfonic anhydride (150 mg, 0.47 mmol) were dissolved in anhydrous pyridine (8.7 mL) under nitrogen and allowed to sit at −10° C. for 24 h. Saturated aqueous sodium bicarbonate solution (10 mL) was added to the reaction mixture, then, stirred for 10 min. The reaction mixture was concentrated in vacuo, then, partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane. The organic extract was separated, washed once again with sodium bicarbonate (aq) and brine, dried over anhydrous sodium sulfate, then concentrated in vacuo. The crude mixture was purified by a silica gel column chromatography [Jones Flashmaster; 10 g column, dry-loaded with silica gel; eluted with 100% DCM to 1:1 EtOAc/DCM to 10% (7N ammonia/MeOH)/chloroform] to obtain the desired mono-tosylated product as a yellow solid; 1H NMR (d6-DMSO, 400 Hz) δ 8.29 (dd, J=8.4, 1.2 Hz, 2H), 8.22 (d, J=1.2 Hz, 1H), 8.19 (d, J=8.8 Hz, 1H), 8.06 (s, 1H), 7.90 (dd, J=8.4, 1.2 Hz, 1H), 7.82 (m, 2H), 7.69 (d, J=5.2 Hz, 1H), 7.563 (m, 2H), 7.50 (m, 3H), 7.08 (d, J=4.8 Hz, 1H), 6.19 (br s, 2H), 3.92 (d, J=5.6 Hz, 2H), 3.10 (m, 1H), 2.08 (s, 3H), 2.44 (s, 3H), 2.00 (m, 2H), 1.77 (m, 2H), 1.66 (m, 2H), 1.20 (m, 2H); MS (ES+): m/z 618.32 (40) [MH+], 426.21 (60) [M-191], 412.52 (100) [M-205]; tR(polar-5 min/MDPS) 3.03 min.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompartitioned between saturated aqueous sodium bicarbonate solution and dichloromethane
  3. extractionThe organic extract
  4. customwas separated
  5. washwashed once again with sodium bicarbonate (aq) and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude mixture was purified by a silica gel column chromatography [Jones Flashmaster; 10 g column, dry-loaded with silica gel; eluted with 100% DCM to 1:1 EtOAc/DCM to 10% (7N ammonia/MeOH)/chloroform]

Sources & evidence

ORD record
ord-52b4ef7d215b4387841af6896f4e7e12
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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