Tetrahydrofuran → 4-(3-Chloro-4-fluorophenyl)-3-(4-[(triisopropylsilyl)oxy]methyl-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

HRID 1845740Notes

Reaction equation

HRID 1845740 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9](O)[C:10]([C:12]2[C:16]([CH2:17][O:18][Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])=[N:15][O:14][N:13]=2)=[NH:11])[CH:5]=[CH:6][C:7]=1[F:8].C1N=CN([C:35](N2C=NC=C2)=[O:36])C=1.[O:42]1CCCC1>>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:35](=[O:36])[O:42][N:11]=[C:10]2[C:12]2[C:16]([CH2:17][O:18][Si:19]([CH:23]([CH3:24])[CH3:25])([CH:26]([CH3:28])[CH3:27])[CH:20]([CH3:21])[CH3:22])=[N:15][O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 682631,1'-Carbonyldiimidazole2×HCID 89676497N-(3-chloro-4-fluorophenyl)-N-hydroxy-4-[(triisopropylsilyl)oxy]methyl-1,2,5-oxadiazole-3-carboximidamide

Product 1

HCID 589417684-(3-Chloro-4-fluorophenyl)-3-(4-[(triisopropylsilyl)oxy]methyl-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-oneYield 73%

Conditions

Temperature
70 °C

Procedure

N-(3-chloro-4-fluorophenyl)-N-hydroxy-4-[(triisopropylsilyl)oxy]methyl-1,2,5-oxadiazole-3-carboximidamide (2.2 g, 5.0 mmol) was dissolved in anhydrous tetrahydrofuran (THF) (31 mL) followed by addition of N,N-carbonyldiimidazole (980 mg, 6 mmol). The reaction was heated to 70° C. and monitored by LCMS. Another 0.5 eq of N,N-carbonyldiimidazole was added and the reaction was stirred overnight at 70° C. The reaction was cooled and concentrated in vacuo. The crude oil was dissolved in chloroform and loaded onto a 120 g ISCO cartridge, eluted with 25% EtOAc/Hexane. The combined fractions were stripped to dryness to give the desired product as a white solid (1.74 g, 73%). 1H NMR (400 MHz, DMSO-d6) δ: 7.95 (m, 1H), 7.65 (m, 1H), 7.64 (m, 1H), 5.12 (s, 2H), 1.14 (m, 3H), 1.04 (d, J=7.0 Hz, 18H); MF=C20H26ClFN4O4Si; LCMS calculated for C20H27ClFN4O4Si(M+H)+: m/z=469.147.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated in vacuo
  3. dissolutionThe crude oil was dissolved in chloroform
  4. washeluted with 25% EtOAc/Hexane

Sources & evidence

ORD record
ord-fc1700d583d844658df2dc8fd52ecfd2
Source dataset
uspto-grants-2015_02
Patent number
US08951536B2

Reaction notes

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