Methanol → 4-Hydroxy-1-(2-morpholin-4-yl-ethyl)-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid 3,5-difluoro-benzylamide

HRID 2214694Notes

Reaction equation

HRID 2214694 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([F:21])[CH:20]=1)[CH2:5][NH:6][C:7](=[O:17])[CH:8]=[C:9]1[C:13](=[O:14])OC(C)(C)[O:10]1.[CH2:22]=[N:23][CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.CO>>[F:21][C:19]1[CH:18]=[C:4]([CH:3]=[C:2]([F:1])[CH:20]=1)[CH2:5][NH:6][C:7]([C:8]1[CH2:22][N:23]([CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:13](=[O:14])[C:9]=1[OH:10])=[O:17]

Participants

4

Reactant 3

HCID 887MethanolHCID 15174513Methylene-(2-morpholin-4-yl-ethyl)-amineHCID 69655928N-(3,5-difluoro-benzyl)-2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetamide

Product 1

HCID 547046754-Hydroxy-1-(2-morpholin-4-yl-ethyl)-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid 3,5-difluoro-benzylamideYield 22%

Procedure

A mixture of N-(3,5-difluoro-benzyl)-2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetamide (60 mg, 0.2 mmol) and a 0.2 mmol solution of methylene-(2-morpholin-4-yl-ethyl)-amine in methanol (1.25 mL, 0.25 mmol) was heated at 70° C. for 1 h. The reaction mixture was cooled to room temperature and purified by preparative HPLC using methanol/water (0.1% TFA) as the eluent. The fractions containing the product were combined and concentrated to give the title compound as a white powder (22 mg, 22% yield). 1H NMR (500 MHz, DMSO) δ: 11.95 (1H, br s), 9.54 (1H, br s), 8.08 (1H, t, J=6.1 Hz), 7.12–7.08 (1H, m), 7.00–6.94 (2H, m), 4.45 (2H, d, J=6.1 Hz), 4.05 (2H, s), 4.02–3.94 (2H, m), 3.83–3.77 (2H, m), 3.69–3.38 (6H, m), 3.16–3.05 (2H, m). HRMS calcd for C18H20F2N3O4 (M−H): 380.1422. found: 380.1422.

Workup

  1. custompurified by preparative HPLC
  2. additionThe fractions containing the product
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-b887b347c8124dae93725f811fbe1de7
Source dataset
uspto-grants-2006_09
Patent number
US07109186B2

Reaction notes

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