Methanesulfonyl chloride → HCID 178505146, compound

HRID 1483853Notes

Reaction equation

HRID 1483853 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:4]=[C:5]([C:9]2[N:13]3[N:14]=[C:15]([NH:18][C@H:19]4[CH2:24][CH2:23][C@H:22]([NH2:25])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.CCN(C(C)C)C(C)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>CS(C)=O>[F:27][C:2]([F:26])([F:1])[C:3]1[CH:4]=[C:5]([C:9]2[N:13]3[N:14]=[C:15]([NH:18][C@H:19]4[CH2:20][CH2:21][C@H:22]([NH:25][S:38]([CH3:37])(=[O:40])=[O:39])[CH2:23][CH2:24]4)[CH:16]=[CH:17][C:12]3=[N:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178511599HCID 178511599, compound

Product 1

HCID 178505146HCID 178505146, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a 0° C. solution of trans-N1-(3-(3-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-6-yl)cyclohexane-1,4-diamine (130 mg, 0.35 mmol) and DIPEA (135.7 mg, 10.5 mmol) in DMSO (1.75 mL) was added dropwise MeSO2Cl (47.6 mg, 0.42 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. 8-90 (30 mg, 18.9%) 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-f8f563db958f4a12957f906e99dc7bfb
Source dataset
uspto-grants-2016_08
Patent number
US09416132B2

Reaction notes

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