4-Toluenesulfonyl chloride → HCID 86709661, compound

HRID 2285366Notes

Reaction equation

HRID 2285366 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:43])[C@@H:24]([NH:26][C:27](=[O:42])[C@@H:28]([NH:32][C:33](=[O:41])[C:34]([CH2:38][CH2:39]O)([CH3:37])[CH:35]=[CH2:36])[CH:29]([CH3:31])[CH3:30])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1>CN(C)C1C=CN=CC=1.ClCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:43])[C@@H:24]([NH:26][C:27](=[O:42])[C@@H:28]([N:32]4[CH2:36][CH2:35][C:34]([CH3:37])([CH:38]=[CH2:39])[C:33]4=[O:41])[CH:29]([CH3:31])[CH3:30])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chloride2×HCID 86709659HCID 86709659, compound

Product 1

HCID 86709661HCID 86709661, compoundYield 42.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-1-((S)-2-{(S)-2-[2-(2-hydroxy-ethyl)-2-methyl-but-3-enoylamino]-3-methyl-butyrylamino}-propionyl)-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (186.4 mg, 0.282 mmol) and 4-dimethylaminopyridine (206.7 mg, 1.692 mmol) in dichloromethane (20 mL) was treated with para-toluenesulfonyl chloride (161.6 mg, 0.848 mmol). After stirring at room temperature for 2.5 h, more 4-dimethylaminopyridine (206.7 mg, 1.692 mmol) and para-toluenesulfonyl chloride (161.6 mg, 0.848 mmol) were added. After stirring at room temperature for 1.5 h, the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 20 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/acetone 1:0 to 3:2 to afford the title compound (77.0 mg, 42%) as a colourless gum and as a 1:1 mixture of diastereoisomers. LCMS (m/z) 643.1 [M+H], Tr=1.90 min and LCMS (m/z) 643.1 [M+H], Tr=1.99 min.

Workup

  1. stirringAfter stirring at room temperature for 1.5 h
  2. customthe volatiles were removed in vacuo
  3. customThe residue was purified by silica gel chromatography
  4. washeluted with a continuous gradient of iso-hexanes/acetone 1:0 to 3:2

Sources & evidence

ORD record
ord-9b196e2be4f842e2b2177c870da0c130
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

Loading…