Acetoxyacetic acid → N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 405794

Reaction equation

HRID 405794 reaction equation
C(C1NC=CN=1)(C1NC=CN=1)=O.C([O:16][CH2:17][C:18]([OH:20])=O)(=O)C.O[N:22]=[C:23]([C:25]1[CH:26]=[CH:27][C:28]([CH3:43])=[C:29]([NH:31][C:32]([C:34]2[N:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]3=[N:36][CH:35]=2)=[O:33])[CH:30]=1)[NH2:24].O.[OH-].[Li+]>CN1C(=O)CCC1.C1COCC1.CO.O>[OH:20][CH2:18][C:17]1[O:16][N:22]=[C:23]([C:25]2[CH:26]=[CH:27][C:28]([CH3:43])=[C:29]([NH:31][C:32]([C:34]3[N:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]4=[N:36][CH:35]=3)=[O:33])[CH:30]=2)[N:24]=1

Participants

7

Reactant 4

HCID 83766Acetoxyacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 86677441N-(5-(N'-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 71280825N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
125 °C

Procedure

Carbonyl diimidazole (CDI) (324 mg, 2.0 mmol) was added to a stirred solution of 2-acetoxyacetic acid (236 mg, 2.0 mmol) in NMP. After 20 minutes, N-(5-(N′-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (9) (310 mg, 1.0 mmol) was added in one portion and the resulting solution was stirred for 1 hour before it was heated at 125° C. for 15 minutes in a microwave reactor. The reaction solution was subjected to standard aqueous work up to afford a residue which was hydrolyzed by lithium hydroxide monohydrate (252 mg, 6.0 mmol) in THF/MeOH/H2O (3:2:1). After removal of all solvents 2M NaHCO3 (10 mL) was added. The precipitate was filtered and dried in air to afford N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (43). 1H NMR (400 MHz, d6-DMSO) δ 10.02 (s, 1H), 9.46 (d, J=6.8 Hz, 1H), 8.59 (s, 1H), 8.11 (s, 1H), 7.82 (m, 2H), 7.53 (m, 2H), 7.18 (m, 1H), 6.08 (m, 1H), 4.80 (d, J=6.0 Hz, 2H), 2.37 (s, 3H). MS m/z 350.1 (M+1)+.

Workup

  1. customto afford a residue which
  2. customAfter removal of all solvents 2M NaHCO3 (10 mL)
  3. additionwas added
  4. filtrationThe precipitate was filtered
  5. customdried in air

Sources & evidence

ORD record
ord-1a905de7e6014d02ba46363e0cbad099
Source dataset
uspto-grants-2014_06
Patent number
US08754071B2

Linked notes

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