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

HRID 2214698Notes

Reaction equation

HRID 2214698 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[F:21])[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:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[F:21])[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 69656094N-(3,4-Difluoro-benzyl)-2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetamide

Product 1

HCID 547046654-Hydroxy-1-(2-morpholin-4-yl-ethyl)-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid 3,4-difluoro-benzylamideYield 31%

Procedure

A mixture of N-(3,4-difluoro-benzyl)-2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetamide (58 mg, 0.195 mmol) and a 0.2 mmol solution of methylene-(2-morpholin-4-yl-ethyl)-amine in methanol (1.1 mL, 0.22 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 hydroscopic yellow powder (30 mg, 31% yield). 1H NMR (500 MHz, DMSO) δ: 11.95 (1H, br s), 9.56 (1H, br s), 8.03 (1H, t, J=6.1 Hz), 7.41–7.30 (2H, m), 7.15–7.12 (1H, m), 4.41 (2H, d, J=6.1 Hz), 4.04 (2H, s), 4.02–3.93 (2H, m), 3.82–3.77 (2H, m), 3.65–3.51 (4H, m), 3.45–3.41 (2H, m), 3.15–3.06 (2H, m). HRMS calcd for C18H20F2N3O4 (M+H): 380.1422. found: 380.1424.

Workup

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

Sources & evidence

ORD record
ord-8ee01c9646f84849a218b1097620eaa4
Source dataset
uspto-grants-2006_09
Patent number
US07109186B2

Reaction notes

Loading…