4-Toluenesulfonyl chloride → HCID 86303767, compound

HRID 869085Notes

Reaction equation

HRID 869085 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:14][CH2:13][C@@:12]34[C:15]5[C:21]6[CH2:22][C@@H:6]2[C@@:7]23[CH2:34][CH2:33][C@:10]([O:35][CH3:36])([C@@H:11]4[O:17][C:16]=5[C:18]([O:23]CC3C=CC(OC)=CC=3)=[CH:19][CH:20]=6)[C@@H:9]([CH2:37][NH2:38])[CH2:8]2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[C:46]1([CH3:56])[CH:51]=[CH:50][C:49]([S:52](Cl)(=[O:54])=[O:53])=[CH:48][CH:47]=1>C(Cl)Cl>[CH:1]1([CH2:4][N:5]2[CH2:14][CH2:13][C@@:12]34[C:15]5[C:21]6[CH2:22][C@@H:6]2[C@@:7]23[CH2:34][CH2:33][C@:10]([O:35][CH3:36])([C@@H:11]4[O:17][C:16]=5[C:18]([OH:23])=[CH:19][CH:20]=6)[C@@H:9]([CH2:37][NH:38][S:52]([C:49]3[CH:50]=[CH:51][C:46]([CH3:56])=[CH:47][CH:48]=3)(=[O:54])=[O:53])[CH2:8]2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 90408658HCID 90408658, compound

Product 1

HCID 86303767HCID 86303767, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Compound 5 (31 mg, 0.06 mmol, 1 eq) in DCM (2 mL) at 0° C. was added triethylamine (86 μL, 6.0 mmol, 10 eq.) followed by p-toluenesulfonyl chloride (34.3 mg, 0.18 mmol, 3 eq.). The reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with DCM and washed with saturated sodium bicarbonate solution. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was evaporated and the crude material dissolved in DCM (2 mL), TFA (0.5 mL) was added and the mixture stirred at 0° C. for 1 h. The residue, after evaporating the solvent, was purified by flash chromatography (SiO2, 1-5% MeOH (with 7% ammonia)/DCM) to provide Compound 124 as the free base. The free base was dissolved in DCM (1 mL) and 1M HCl in Et2O (1 mL) was added and the mixture stirred at 0° C. for 1 h. The solvents were evaporated and the residue was triturated with Et2O to give Compound 124 HCl salt as a white solid

Workup

  1. washwashed with saturated sodium bicarbonate solution
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe solvent was evaporated
  5. dissolutionthe crude material dissolved in DCM (2 mL)
  6. additionTFA (0.5 mL) was added
  7. stirringthe mixture stirred at 0° C. for 1 h
  8. customThe residue, after evaporating the solvent
  9. customwas purified by flash chromatography (SiO2, 1-5% MeOH (with 7% ammonia)/DCM)

Sources & evidence

ORD record
ord-5abccf4c6ecd4a28b0cd8c5e2685c0fd
Source dataset
uspto-grants-2015_03
Patent number
US08969358B2

Reaction notes

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