Diisopropylethylamine → HCID 11490818, compound

HRID 2373805Notes

Reaction equation

HRID 2373805 reaction equation
Cl[C:2]([C:4]1[CH:5]=[C:6]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:7]=[CH:8][C:9]=1[O:10]C(=O)C)=[O:3].Cl.[CH2:25]([O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([CH2:45][C@@H:46]([NH2:53])[C:47]3[O:51][N:50]=[C:49]([CH3:52])[N:48]=3)=[CH:41][CH:40]=2)=[CH:35][C:34]=1[F:54])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C>>[CH2:25]([O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([CH2:45][C@@H:46]([NH:53][C:2]([C:4]3[CH:5]=[C:6]([C:14]4[CH:15]=[CH:16][C:17]([C:20]([F:22])([F:21])[F:23])=[CH:18][CH:19]=4)[CH:7]=[CH:8][C:9]=3[OH:10])=[O:3])[C:47]3[O:51][N:50]=[C:49]([CH3:52])[N:48]=3)=[CH:41][CH:40]=2)=[CH:35][C:34]=1[F:54])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 69207153HCID 69207153, compoundHCID 86032175HCID 86032175, compound

Product 1

HCID 11490818HCID 11490818, compound

Procedure

4-Hydroxy-4′-trifluoromethyl-biphenyl-3-carboxylic acid [(4′-benzyloxy-3′-fluoro-biphenyl-4-yl)-1-(R)-(3-methyl-[1,2,4]oxadiazol-5-yl)-ethyl]-amide (58 mg) was prepared from acetic acid 3-chlorocarbonyl-4′-trifluoromethyl-biphenyl-4-yl ester (1.96 mL, 0.1 M CH2Cl2), 2-(4′-benzyloxy-3′-fluoro-biphenyl-4-yl)-1-(R)-(3-methyl-[1,2,4]oxadiazol-5-yl)-ethylamine hydrochloride (90 mg, 0.178 mmol) and DIEA (95 μL, 0.55 mmol) analogous to procedure M. The crude reaction mixture was concentrated and redissolved in THF (3 mL) and MeOH (1 mL). 1N NaHCO3 (200 μL) and 1 N Na2CO3 (50 μL) were added and the hydrolysis was followed by TLC and LCMS. Once complete, the reaction was diluted with EtOAc and the layers were separated. After extraction and drying the combined organics over MgSO4, the crude mixture was concentrated onto silica gel and purified by chromatography using 15% EtOAc in hexanes.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated
  3. dissolutionredissolved in THF (3 mL)
  4. addition1N NaHCO3 (200 μL) and 1 N Na2CO3 (50 μL) were added
  5. additionOnce complete, the reaction was diluted with EtOAc
  6. customthe layers were separated
  7. extractionAfter extraction
  8. dry with materialdrying the combined organics over MgSO4
  9. concentrationthe crude mixture was concentrated onto silica gel
  10. custompurified by chromatography

Sources & evidence

ORD record
ord-5d5c35f043524483b78d98d55c889a12
Source dataset
uspto-grants-2008_12
Patent number
US07459472B2

Reaction notes

Loading…