N-Methylisopropylamine → 3-[2-Ethyl-4-(5-{5-[(isopropyl-methyl-amino)-methyl]-4-methyl-thiophen-2-yl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenyl]-propionic acid

HRID 1685752Notes

Reaction equation

HRID 1685752 reaction equation
C(OC(=O)CCC1C(C)=CC(C2N=C(C3SC(C=O)=C(C)C=3)ON=2)=CC=1CC)C.C(NC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)=O.C([O:54][C:55](=[O:84])[CH2:56][CH2:57][C:58]1[C:63]([CH3:64])=[CH:62][C:61]([C:65]2[N:69]=[C:68]([C:70]3[S:71][C:72]([CH2:76][N:77]([CH:79]([CH3:81])[CH3:80])[CH3:78])=[C:73]([CH3:75])[CH:74]=3)[O:67][N:66]=2)=[CH:60][C:59]=1[CH2:82][CH3:83])C>C(O)C.[OH-].[Na+]>[CH2:82]([C:59]1[CH:60]=[C:61]([C:65]2[N:69]=[C:68]([C:70]3[S:71][C:72]([CH2:76][N:77]([CH:79]([CH3:81])[CH3:80])[CH3:78])=[C:73]([CH3:75])[CH:74]=3)[O:67][N:66]=2)[CH:62]=[C:63]([CH3:64])[C:58]=1[CH2:57][CH2:56][C:55]([OH:84])=[O:54])[CH3:83]

Participants

7

Reactant 4

HCID 78485N-MethylisopropylamineHCID 5049666Sodium triacetoxyborohydrideHCID 672656273-[2-Ethyl-4-(5-{5-[(isopropyl-methyl-amino)-methyl]-4-methyl-thiophen-2-yl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenyl]-propionic acid ethyl ester formate saltHCID 866464453-{2-Ethyl-4-[5-(5-formyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid ethyl ester

Product 1

HCID 672653143-[2-Ethyl-4-(5-{5-[(isopropyl-methyl-amino)-methyl]-4-methyl-thiophen-2-yl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenyl]-propionic acidYield 96.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

3-[2-Ethyl-4-(5-{5-[(isopropyl-methyl-amino)-methyl]-4-methyl-thiophen-2-yl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenyl]-propionic acid ethyl ester formate salt (86 mg) is obtained as a pale yellow oil starting from 3-{2-ethyl-4-[5-(5-formyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid ethyl ester (100 mg, 0.242 mmol) and N-isopropyl-methylamine (709 mg, 9.70 mmol) using two portions of sodium triacetoxyborohydride (171 mg, 0.727 mmol) and following Method C; LC-MS: tR=0.71 min; [M+1]+=470.15; 1H NMR (D6-DMSO): δ1.05 (d, J=6.5 Hz, 6H), 1.17-1.26 (m, 6H), 2.23 (s, 6H), 2.39 (s, 3H), 2.44-2.50 (m, 2H), 2.72 (q, J=7.5 Hz, 2H), 2.89-3.01 (m, 3H), 3.70 (s, 2H), 4.10 (q, J=7.0 Hz, 2H), 7.69 (s, 2H), 7.80 (s, 1H), 8.15 (s, 1H). b) A solution of the above propionic acid ethyl ester (75 mg, 0.145 mmol) in ethanol (1.5 mL) and 2 N aq. NaOH (1.5 mL) is stirred at rt for 6 h. The ethanol is evaporated and the reaction mixture is acidified by adding formic acid before it is separated be prep. HPLC (column: Atlantis T3 C18, 30×75 mm, 10 μm, eluting with a gradient of acetonitrile in water containing 0.5% of formic acid) to give the title compound (62 mg) as its formate salt as a pale yellow solid; LC-MS*: tR=0.66 min; [M−1]−=440.02; 1H NMR (D6-DMSO): δ1.05 (d, J=6.5 Hz, 6H), 1.22 (t, J=7.3 Hz, 3H), 2.23 (s, 6H), 2.33-2.42 (m, 5H), 2.73 (q, J=7.5 Hz, 2H), 2.89-2.97 (m, 3H), 3.70 (s, 2H), 7.69 (s, 2H), 7.80 (s, 1H), 8.17 (s, 1H).

Workup

  1. customThe ethanol is evaporated
  2. additionby adding formic acid before it
  3. customis separated
  4. washHPLC (column: Atlantis T3 C18, 30×75 mm, 10 μm, eluting with a gradient of acetonitrile in water containing 0.5% of formic acid)

Sources & evidence

ORD record
ord-05e88c1aa88a4380897fddac948edacf
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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