Diisopropylcarbodiimide → HCID 56948654, compound

HRID 714267Notes

Reaction equation

HRID 714267 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:15][CH2:16][C:17](O)=[O:18])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.O/[N:21]=[C:22](/[C:24]1[CH:29]=[CH:28][NH:27][C:26](=[O:30])[CH:25]=1)\[NH2:23].C(N=C=NC(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(#N)C.CCOC(C)=O>[F:8][C:6]1[CH:5]=[C:4]([C:9]2([CH2:15][CH2:16][C:17]3[O:18][N:23]=[C:22]([C:24]4[CH:29]=[CH:28][NH:27][C:26](=[O:30])[CH:25]=4)[N:21]=3)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

7

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 2724141Tetrabutylammonium FluorideHCID 43165089HCID 43165089, compoundHCID 66824535HCID 66824535, compound

Product 1

HCID 56948654HCID 56948654, compoundYield 16.64%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(1-(3,5-difluorophenyl)cyclohexyl)propanoic acid (20 mg, 0.075 mmol) and (Z)—N′-hydroxy-2-oxo-1,2-dihydropyridine-4-carboximidamide (11.42 mg, 0.075 mmol) in acetonitrile (1 mL) was added N,N′-diisopropylcarbodiimide (0.013 mL, 0.082 mmol), and the mixture was stirred for 2.5 hrs at room temp. TBAF (0.112 mL, 0.112 mmol) was added and the mixture was stirred for 40 hrs at room temp. After addition of EtOAc the mixture was washed with water and brine, dried over Na2SO4 and evaporated to give an oily residue which was purified by Combiflash (12 g silica gel). Elution with 7:93 MeOH—CH2Cl2 gave a white solid residue which was repurified by prep HPLC to give 4-(5-(2-(1-(3,5-difluorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)pyridin-2(1H)-one (4.8 mg, 16.64% yield) as a white solid. HPLC: tR=3.95 min, Waters Sunfire C18 4.6×50 mm, 4 min gradient, Detection Wave length 220 nm, Starting solvent: 10% aq. MeOH-0.1% TFA; Final solvent: 90% aq. MeOH-0.1% TFA. LC/MS: m/e 386.13 (M+H)+. 1H NMR (400 MHz, CDCl3): δ ppm 7.45 (1 H, d), 7.24 (1H, s), 6.84-6.88 (3 H, m), 6.65 (1H, m), 2.56-2.6 (2 H, m), 2.05-2.07 (4 H, m), 1.23-1.63 (8 H, m).

Workup

  1. stirringthe mixture was stirred for 40 hrs at room temp
  2. washwas washed with water and brine
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customto give an oily residue which
  6. customwas purified by Combiflash (12 g silica gel)
  7. washElution with 7:93 MeOH—CH2Cl2
  8. customgave a white solid residue which
  9. customwas repurified by prep HPLC

Sources & evidence

ORD record
ord-76fa4ca7b0cc4657b1db25af7140bac6
Source dataset
uspto-grants-2015_11
Patent number
US09187437B2

Reaction notes

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