Trifluoroacetic acid → HCID 68732367, compound

HRID 1685767Notes

Reaction equation

HRID 1685767 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][CH2:24][NH2:25])=[CH:19][CH:18]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:26])[CH2:4][CH3:5])[CH3:2].[C:27]([O:31][C:32]([N:34]([CH2:36][C:37]([OH:39])=[O:38])[CH3:35])=[O:33])([CH3:30])([CH3:29])[CH3:28].C(O)(C(F)(F)F)=O>C(Cl)Cl.CC(=O)OCC>[C:27]([O:31][C:32](=[O:33])[N:34]([CH2:36][C:37](=[O:38])[NH:25][CH2:24][CH2:23][C:20]1[CH:19]=[CH:18][C:17]([C:14]2[N:13]=[C:12]([C:10]3[S:11][C:7]([CH2:6][N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[C:8]([CH3:26])[CH:9]=3)[O:16][N:15]=2)=[CH:22][CH:21]=1)[CH3:35])([CH3:30])([CH3:28])[CH3:29].[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][CH2:24][NH:25][C:37](=[O:39])[CH2:36][NH:34][CH3:35])=[CH:21][CH:22]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:26])[CH2:4][CH3:5])[CH3:2]

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 67265437HCID 67265437, compound

Product 2

HCID 68732367HCID 68732367, compoundYield 100.6%HCID 86646456HCID 86646456, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

[(2-{4-[5-(5-Diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethylcarbamoyl)-methyl]-methyl-carbamic acid tert-butyl ester is prepared in analogy to Example 163 by coupling 2-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethylamine (20 mg, 54 μmol) with (tert-butoxycarbonyl-methyl-amino)-acetic acid (15 mg, 81 μmol); LC-MS: tR=0.84 min; [M+1]+=542.20; 1H NMR (CDCl3): δ1.16 (m, 6H), 1.44 (s, 9H), 2.27 (s, 3H), 2.88 (s, 3H), 2.90-2.99 (m, 2H), 3.61 (q, J=6.5 Hz, 2H), 3.75 (s br, 1H), 3.85 (s, 2H), 7.34 (d, J=8.0 Hz, 2H), 7.67 (s, 1H), 8.10 (d, J=8.0 Hz, 2H). This material (18 mg, 30 μmol) is dissolved in DCM (2 mL) and TFA (50 μL) is added. The mixture is stirred at rt for 18 h before it is diluted with EA and washed with sat. aq. NaHCO3 solution. The organic extract is dried over Na2SO4, filtered and concentrated. The crude product is purified by prep. HPLC and on prep. TLC plates with DCM containing 10% of 7 N NH3 in methanol to give the title compound (12 mg) as a colourless solid; LC-MS: tR=0.64 min; [M+1]+=442.00.

Workup

  1. washwashed with sat. aq. NaHCO3 solution
  2. extractionThe organic extract
  3. dry with materialis dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-e9adf66d9d4b4b4f9d238ac45e9f4dc5
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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