Potassium Carbonate → 5-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

HRID 634112Notes

Reaction equation

HRID 634112 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[O:21][C:20]([NH:22][CH2:23][C:24]5[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=5)=[N:19][N:18]=4)[CH:15]=3)[N:10]([S:32]([C:35]3[CH:41]=[CH:40][C:38]([CH3:39])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[CH:9]=2)[N:3]=1.[F:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[O:21][C:20]([NH:22][CH2:23][C:24]5[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=5)=[N:19][N:18]=4)[CH:15]=3)[N:10]([S:32]([C:35]3[CH:41]=[CH:40][C:38]([CH3:39])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[CH:9]=2)[N:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 867250935-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 683280415-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amineYield 72.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a solution of 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (500 mg, 0.85 mmol) and 2-fluorophenylboronic acid (143.5 mg, 1.02 mmol) in p-dioxane/H2O (3:1, 15 mL) was added K2CO3 (235.5 mg, 1.71 mmol) and Pd(PPh3)4 (49 mg, 0.0427 mmol). The reaction was heated at reflux for 24 h, quenched with H2O and extracted with EtOAc. The combined organic layers were dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 50% EtOAc in Hex) to give to 5-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (400 mg, 72.8%). MS (ESI, pos. ion) m/z: 647.1 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 9.43 (s, 1H), 9.06-8.97 (m, 2H), 8.42-8.17 (m, 2H), 8.12-8.03 (m, 3H), 7.91 (dd, J=8, 1.6 Hz, 1H), 7.65-7.53 (m, 5H), 7.46-7.40 (m, 4H), 7.28 (m, 2H), 6.88 (d, J=8 Hz, 2H), 4.35 (d, J=8 Hz, 2H), 3.72 (s, 3H), 2.33 (s, 3H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 h
  3. customquenched with H2O
  4. extractionextracted with EtOAc
  5. customThe combined organic layers were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography (eluting with 50% EtOAc in Hex)

Sources & evidence

ORD record
ord-3f0d14229e1d404894acdb1aacf45e1a
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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