Methanesulfonyl chloride → HCID 178505149, compound

HRID 1483854Notes

Reaction equation

HRID 1483854 reaction equation
[F:1][C:2]([F:28])([F:27])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[N:14]3[N:15]=[C:16]([NH:19][C@H:20]4[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]4)[CH:17]=[CH:18][C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1.CCN(C(C)C)C(C)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>CS(C)=O>[F:28][C:2]([F:1])([F:27])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[N:14]3[N:15]=[C:16]([NH:19][C@H:20]4[CH2:21][CH2:22][C@H:23]([NH:26][S:39]([CH3:38])(=[O:41])=[O:40])[CH2:24][CH2:25]4)[CH:17]=[CH:18][C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178511602HCID 178511602, compound

Product 1

HCID 178505149HCID 178505149, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a 0° C. solution of trans-N1-(3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-yl)cyclohexane-1,4-diamine (180 mg, 0.46 mmol) and DIPEA (178 mg, 1.38 mol) in DMSO (2.0 mL) was added dropwise MeSO2Cl (53 mg, 0.46 mmol). The resulting mixture was stirred at room temperature overnight. LCMS showed most of starting material was converted. The mixture was partitioned between brine (100 mL) and EtOAc (50 mL) and separated. The aqueous layer was extracted with EtOAc (50 mL*3). The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-HPLC to give EX. 8-91 (57.1 mg, 26.4%) as a white solid.

Workup

  1. customThe mixture was partitioned between brine (100 mL) and EtOAc (50 mL)
  2. customseparated
  3. extractionThe aqueous layer was extracted with EtOAc (50 mL*3)
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by prep-HPLC
  8. customto give EX

Sources & evidence

ORD record
ord-37309b13a6734b41b12ea6a2406da139
Source dataset
uspto-grants-2016_08
Patent number
US09416132B2

Reaction notes

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