Methanesulfonyl chloride → HCID 86646454, compound

HRID 1685756Notes

Reaction equation

HRID 1685756 reaction equation
[CH2:1]([N:3]([CH2:6][C:7]1[S:11][C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:25])[CH2:4][CH3:5])[CH3:2].CCN(C(C)C)C(C)C.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>C(Cl)Cl>[CH2:1]([N:3]([CH2:6][C:7]1[S:11][C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([CH2:23][O:24][S:36]([CH3:35])(=[O:38])=[O:37])=[CH:21][CH:22]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:25])[CH2:4][CH3:5])[CH3:2]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67265388HCID 67265388, compound

Product 1

HCID 86646454HCID 86646454, compoundYield 124.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of {4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-methanol (971 mg, 2.72 mmol) in DCM (40 mL), DIPEA (526 mg, 4.07 mmol) and methanesulfonyl chloride (373 mg, 3.26 mmol) is added. The reaction mixture is stirred at rt for 15 h before it is diluted with DCM and washed with sat. aq. NaHCO3 solution. The washing is extracted back three times with DCM. The combined organic extracts are dried over MgSO4, filtered, concentrated and dried to give crude methanesulfonic acid 4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-benzyl ester (1.48 g) as an orange solid containing {5-[3-(4-chloromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-thiophen-2-ylmethyl}-diethyl-amine; LC-MS: tR=0.58 min; [M+1]+=436.11. b) A solution of the above crude methanesulfonic acid 4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-benzyl ester (248 mg, 0.569 mmol) in 7 N NH3 in methanol (10 mL) is stirred in a sealed vial at 80° C. for 16 h. The solvent is removed in vacuo and the residue is dissolved in EA and washed with brine and water. The organic extract is dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates with DCM containing 5% of 7N NH3 in methanol to give the title compound (137 mg) as a pale yellow oil; LC-MS: tR=0.38 min; [M+1]+=357.30; 1H NMR (CDCl3): δ 1.11 (t, J=7.0 Hz, 6H), 2.26 (s, 3H), 2.64 (q, J=7.0 Hz, 4H), 3.73 (s, 2H), 3.98 (s, 2H), 7.47 (d, J=7.8 Hz, 2H), 7.67 (s, 1H), 8.13 (d, J=7.5 Hz, 2H).

Workup

  1. washwashed with sat. aq. NaHCO3 solution
  2. extractionThe washing is extracted back three times with DCM
  3. dry with materialThe combined organic extracts are dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customdried

Sources & evidence

ORD record
ord-774281ae293f4b4989e46c4315b6e56e
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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