Ethanolamine → 1-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]-N-(2-hydroxyethyl)piperidine-3-carboxamide

HRID 1727033Notes

Reaction equation

HRID 1727033 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]=2[N:7]=[C:6]1[N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24](O)=[O:25])[CH2:19]1.[NH2:32][CH2:33][CH2:34][OH:35].CCOC(C)=O.CO>C(Cl)Cl>[Cl:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]=2[N:7]=[C:6]1[N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:32][CH2:33][CH2:34][OH:35])=[O:25])[CH2:19]1

Participants

6

Reactant 4

HCID 700EthanolamineHCID 887MethanolHCID 8857Ethyl AcetateHCID 100038741-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylic acid

Product 1

HCID 575656011-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]-N-(2-hydroxyethyl)piperidine-3-carboxamideYield 33.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-[7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylic acid (30 mg, 0.066 mmol) in 1.0 mL of CH2Cl2 at room temperature was treated with polystyrene-carbodiimide (1.15 mmol/g, 104 mg, 0.12 mmol) and stirred for 30 min. The reaction mixture was treated with 2-aminoethanol (0.004 mL, 0.066 mmol), allowed to rotate overnight, filtered, and concentrated in vacuo. The crude product was purified by preparative TLC chromatography eluting with 5:5:1/hexanes:EtOAc:MeOH to give 11 mg (33% yield) of the title compound: 1H NMR (CDCl3, 400 MHz) δ 7.26-7.14 (m, 2H), 7.00-6.93 (m, 1H), 6.17 (br s), 5.58 (d, 2H, J=1.5), 3.70 (t, 2H, J=5.1), 3.51 (s, 3H), 3.47-3.36 (m, 3H), 3.31 (s, 3H), 3.23 (br d, 1H, J=12.3), 3.12 (dd, 1H, J=12.8, 10.3), 2.97-2.88 (m, 1H), 2.42-2.32 (m, 1H), 1.94-1.86 (m, 1H), 1.82-1.45 (m, 4H); LRMS (ESI) m/z 493 (M+H+); TLC (hexanes:EtOAc:MeOH/5:5:1) Rf=0.12.

Workup

  1. waitto rotate overnight
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by preparative TLC chromatography
  5. washeluting with 5:5:1/hexanes

Sources & evidence

ORD record
ord-d088c0264592410699cd9e4bf10aa9bb
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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