Dimethylformamide → Methyl 2-(4-chloro-6-(4-methoxybenzylamino)pyrimidin-5-yl)acetate

HRID 1685191Notes

Reaction equation

HRID 1685191 reaction equation
Cl[C:2]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:6]([Cl:13])[N:5]=[CH:4][N:3]=1.CN(C=O)C.[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C>>[Cl:13][C:6]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:2]([NH:26][CH2:25][C:24]2[CH:27]=[CH:28][C:21]([O:20][CH3:19])=[CH:22][CH:23]=2)[N:3]=[CH:4][N:5]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 54165419Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate

Product 1

HCID 86641609Methyl 2-(4-chloro-6-(4-methoxybenzylamino)pyrimidin-5-yl)acetateYield 84.5%

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 2-(4,6-dichloropyrimidin-5-yl)acetate (1.00 equiv; 65.10 mmol; 14.39 g) in DMF (0.5 M; 1.68 mol; 130.20 mL), add 4-methoxybenzylamine (1.10 equiv; 71.61 mmol; 9.36 mL) and DIPEA (1.20 equiv; 78.12 mmol; 13.62 mL) and stir the mixture at 60° C. for 1 h. Quench with ice-water, extract with EA, and wash the organic layer with 1N HCl, water and brine, dry over MgSO4, filter and concentrate in vacuo to the title compound (54.98 mmol; 17.69 g; 84.45%) as a yellow solid and use without further purification. 1H NMR (300 MHz, DMSO): 8.20 (s, 1H), 7.21-7.18 (m, 2H), 6.89-6.85 (m, 2H), 4.53 (d, J=5.8 Hz, 2H), 3.76 (s, 2H), 3.71 (s, 3H).

Workup

  1. customQuench with ice-water
  2. extractionextract with EA
  3. washwash the organic layer with 1N HCl, water and brine
  4. dry with materialdry over MgSO4
  5. filtrationfilter

Sources & evidence

ORD record
ord-21ce8b359c68486e924943eb1aef41e9
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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