HCID 67265247, compound → HCID 67265704, compound

HRID 1685757Notes

Reaction equation

HRID 1685757 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]=[C:12]([C:14]3[S:18][C:17]([CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[C:16]([CH3:25])[CH:15]=3)[O:11][N:10]=2)=[CH:5][CH:4]=1.C([N:28](CC1SC(C2ON=C(C3C=CC(COS(C)(=O)=O)=CC=3)N=2)=CC=1C)CC)C>N.CO>[NH2:28][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]=[C:12]([C:14]3[S:18][C:17]([CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[C:16]([CH3:25])[CH:15]=3)[O:11][N:10]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 67265247HCID 67265247, compoundHCID 86646454HCID 86646454, compound

Product 1

HCID 67265704HCID 67265704, compound

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 887MethanolSolvent

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. customThe solvent is removed in vacuo
  2. dissolutionthe residue is dissolved in EA
  3. washwashed with brine and water
  4. extractionThe organic extract
  5. dry with materialis dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-a62684eaef06475e97123b6786c9775b
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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