Sodium Hydroxide → 2-(2,6-Difluorophenyl)-5-(4-(3-(methylamino)propanamido)phenylamino)oxazole-4-carboxamide

HRID 1410514Notes

Reaction equation

HRID 1410514 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([C:29]2[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:30]=2[F:36])[O:6][C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:28])[CH2:17][CH2:18][N:19]([CH3:27])C(=O)OC(C)(C)C)=[CH:11][CH:10]=1)#[N:2].C(=O)(O)[O-:38].[Na+].[OH-].[Na+]>S(=O)(=O)(O)O>[F:35][C:34]1[CH:33]=[CH:32][CH:31]=[C:30]([F:36])[C:29]=1[C:5]1[O:6][C:7]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:28])[CH2:17][CH2:18][NH:19][CH3:27])=[CH:11][CH:10]=2)=[C:3]([C:1]([NH2:2])=[O:38])[N:4]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 59587674Tert-butyl 3-(4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)phenylamino)-3-oxopropyl(methyl)carbamate

Product 1

HCID 595874732-(2,6-Difluorophenyl)-5-(4-(3-(methylamino)propanamido)phenylamino)oxazole-4-carboxamideYield 22%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

A solution of tert-butyl 3-(4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)phenylamino)-3-oxopropyl(methyl)carbamate (0.021 g, 0.04 mmol) in concentrated sulfuric acid (1 ml) was stirred at room temperature overnight. The reaction was basified by addition to sat. sodium bicarbonate and then addition of 6M NaOH (to ˜pH12). The aqueous phase was then extracted with EtOAc, the combined organic phases dried over MgSO4 and the solvent removed in vacuo. The residue was purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(4-(3-(methylamino)propanamido)phenylamino)oxazole-4-carboxamide (0.0038 g, 0.009 mmol, 22%). 1H NMR (CD3OD) δ 2.64 (3H, s), 2.73 (2H, t), 3.20 (2H, masked by CD3OD peak), 7.08 (2H, t), 7.29 (2H, d), 7.45 (1H, m), 7.48 (2H, d), 8.45 (1H, br. s). LCMS (2) Rt: 2.28 min; m/z (ES+) 416.

Workup

  1. extractionThe aqueous phase was then extracted with EtOAc
  2. dry with materialthe combined organic phases dried over MgSO4
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-e73fad6ff31e444ea07b0e7e9b6a0703
Source dataset
uspto-grants-2014_12
Patent number
US08921544B2

Reaction notes

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