Benzyloxyacetyl chloride → 2-benzyloxy-N-{2-chloro-4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-acetamide

HRID 1685778Notes

Reaction equation

HRID 1685778 reaction equation
[CH2:1]([O:8][CH2:9][C:10](Cl)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:13][C:14]1[CH:19]=[C:18]([C:20]2[N:24]=[C:23]([C:25]3[S:26][C:27]([CH2:31][N:32]([CH2:35][CH3:36])[CH2:33][CH3:34])=[C:28]([CH3:30])[CH:29]=3)[O:22][N:21]=2)[CH:17]=[C:16]([CH3:37])[C:15]=1[NH2:38]>C(Cl)Cl.C(OCC)C>[CH2:1]([O:8][CH2:9][C:10]([NH:38][C:15]1[C:16]([CH3:37])=[CH:17][C:18]([C:20]2[N:24]=[C:23]([C:25]3[S:26][C:27]([CH2:31][N:32]([CH2:33][CH3:34])[CH2:35][CH3:36])=[C:28]([CH3:30])[CH:29]=3)[O:22][N:21]=2)=[CH:19][C:14]=1[Cl:13])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 177085Benzyloxyacetyl chlorideHCID 672658962-Chloro-4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenylamine

Product 1

HCID 672657752-benzyloxy-N-{2-chloro-4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-acetamideYield 28.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of benzyloxyacetyl chloride (142 mg, 767 μmol) in DCM (2 mL) is added to a solution of 2-chloro-4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenylamine (30 mg, 77 μmol) in DCM (2 mL). The mixture is stirred at rt for 15 h. The mixture is diluted with diethyl ether and washed with 1 N aq. HCl. The organic extract is washed with 33% aq. KOH solution, dried over MgSO4, filtered and concentrated. The crude product is purified by reverse phase MPLC to give 2-benzyloxy-N-{2-chloro-4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-acetamide (12 mg) as a pale yellow oil; LC-MS: tR=0.68 min; [M+1]+=529.18. The material is dissolved in THF:ethanol 1:1 (5 mL) and Pd/C (10 mg, 10% Pd) is added. The mixture is stirred at rt for 15 h under 5 bar of H2. The catalyst is removed by filtration and the filtrate is concentrated. The crude product is purified on prep. TLC plates with DCM containing 4% of methanol to give the title compound (4 mg) as a white solid; LC-MS: tR=0.50 min; [M+1]+=448.98; 1H NMR (CD3OD): δ 1.13 (t, J=7.0 Hz, 6H), 2.29 (s, 3H), 2.39 (s, 3H), 2.66 (q, J=6.8 Hz, 4H), 3.80 (s, 2H), 4.24 (s, 2H), 7.75 (s, 1H), 8.00 (s, 1H), 8.06 (s, 1H).

Workup

  1. washwashed with 1 N aq. HCl
  2. extractionThe organic extract
  3. washis washed with 33% aq. KOH solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by reverse phase MPLC

Sources & evidence

ORD record
ord-09f4f97b063c4171adab00c39261ce9b
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

Loading…