Methanesulfonyl chloride → HCID 56932630, compound

HRID 1972525Notes

Reaction equation

HRID 1972525 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]#[C:11][C:12]1[CH:13]=[C:14]([C:32]([OH:41])([C:37]([F:40])([F:39])[F:38])[C:33]([F:36])([F:35])[F:34])[CH:15]=[CH:16][C:17]=1[N:18]1[CH2:23][CH2:22][N:21]([S:24]([C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)(=[O:26])=[O:25])[CH2:20][CH2:19]1.C(N(C(C)C)CC)(C)C.[CH3:51][S:52](Cl)(=[O:54])=[O:53]>C(Cl)Cl>[S:28]1[CH:29]=[CH:30][CH:31]=[C:27]1[S:24]([N:21]1[CH2:22][CH2:23][N:18]([C:17]2[CH:16]=[CH:15][C:14]([C:32]([OH:41])([C:37]([F:39])([F:40])[F:38])[C:33]([F:34])([F:35])[F:36])=[CH:13][C:12]=2[C:11]#[C:10][CH2:9][NH:8][S:52]([CH3:51])(=[O:54])=[O:53])[CH2:19][CH2:20]1)(=[O:26])=[O:25]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 56932574HCID 56932574, compound

Product 1

HCID 56932630HCID 56932630, compoundYield 55.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(3-(3-amino-1-propyn-1-yl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol trifluoroacetate (102 mg, 0.17 mmol, Example 159) in CH2Cl2 (4 mL) was added diisopropylethylamine (89 μL, 0.51 mmol) and methanesulfonyl chloride (14 μL, 0.19 mmol). The reaction mixture was stirred at room temperature for 20 min and then partitioned between CH2Cl2 (5 mL) and saturated aqueous sodium bicarbonate (5 mL). The layers were separated, the organic material was separated, washed with saturated aqueous sodium bicarbonate (5 mL), dried (Na2SO4), filtered, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by column chromatography (12 g of silica gel, 10% to 50% EtOAc in hexanes) to provide N-(3-(2-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-2-propyn-1-yl)methanesulfonamide (57 mg) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.72 (br s, 1H), 8.09 (br s, 1H), 7.48-7.78 (m, 4H), 7.32 (br s, 1H), 7.11 (d, J=7.63 Hz, 1H), 4.07 (br s, 2H), 3.41-3.32 (m., 4H), 3.21-3.05 (m, 4H), 2.93 (s, 3H); m/z (ESI, +ve ion) 606.0 (M+H)+. GK-GKRP IC50 (Binding)=0.783 μM. GK-GKRP EC50 (LC MS/MS-2)=0.412 μM.

Workup

  1. custompartitioned between CH2Cl2 (5 mL) and saturated aqueous sodium bicarbonate (5 mL)
  2. customThe layers were separated
  3. customthe organic material was separated
  4. washwashed with saturated aqueous sodium bicarbonate (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by column chromatography (12 g of silica gel, 10% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2a5802eaee5d42f5ad3b44dc6585a9b9
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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