Dimethylformamide → HCID 25001823, compound

HRID 1172924Notes

Reaction equation

HRID 1172924 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20](F)=[CH:19][CH:18]=3)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH2:24][C@H:25]1[CH2:29][CH2:28][C@@H:27]([C:30]([OH:32])=[O:31])[CH2:26]1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>CS(C)=O.CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([NH:24][C@H:25]4[CH2:29][CH2:28][C@@H:27]([C:30]([OH:32])=[O:31])[CH2:26]4)=[CH:19][CH:18]=3)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 150203549805-32-5HCID 59556688HCID 59556688, compound

Product 1

HCID 25001823HCID 25001823, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

3-(3-Chloro-4-isopropoxyphenyl)-5-(4-fluorophenyl)-1,2,4-oxadiazole (360 mg, 1.082 mmol), (1R,3S)-3-aminocyclopentanecarboxylic acid (154 mg, 1.190 mmol), potassium carbonate (329 mg, 2.380 mmol) and DMF (2 ml) was heated with cooling at 160° C. on the Biotage microwave for 30 minutes. The mixture was diluted with DMSO (6 ml) and MeCN (8 ml), filtered and divided into 8 aliquots for purification by molecular ion directed LCMS. The fractions were combined and evaporated to afford a pale brown solid that was dried in vacuo at about 60° C. for about 3 hours. This gave (1R,3S)-3-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenylamino)cyclopentanecarboxylic acid (212 mg, 0.480 mmol, 44.3% yield) as a pale brown solid. LCMS (Table 1, Method a) Rt=3.49 min, m/z 440.20 (M−H)−. 1H NMR (400 MHz, DMSδ ppm 4.81 (s, 1H), 3.96-3.76 (m, 1H), 2.78 (s, 1H), 2.42-2.25 (m, 1H), 2.12-1.95 (m, 1H), 1.89 (d, J=7.72 Hz, 2H), 1.73-1.61 (m, 1H), 1.61-1.48 (m, 1H), 1.39-1.30 (m, 7H), 12.22-12.07 (m, 1H), 6.73 (d, J=8.82 Hz, 2H), 6.87-6.79 (m, 1H), 7.36 (d, J=8.63 Hz, 1H), 7.87 (d, J=8.59 Hz, 2H), 7.98 (ddd, J=9.78, 1.97, 1.06 Hz, 2H).

Workup

  1. filtrationfiltered
  2. customdivided into 8 aliquots for purification by molecular ion
  3. customevaporated
  4. customto afford a pale brown solid that
  5. customwas dried in vacuo at about 60° C. for about 3 hours

Sources & evidence

ORD record
ord-3ccf21f0e5e64c69950297ee63fc721d
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

Loading…