4-Methoxybenzylamine → HCID 10647359, compound

HRID 1520737Notes

Reaction equation

HRID 1520737 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18](F)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH2:28])=[CH:25][CH:24]=1>CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH:28][CH2:27][C:26]4[CH:29]=[CH:30][C:23]([O:22][CH3:21])=[CH:24][CH:25]=4)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 10616889HCID 10616889, compound

Product 1

HCID 10647359HCID 10647359, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of compound 162 (13.9 g, 41.3 mmol) and 4-methoxybenzylamine (54.3 mL, 413 mmol) in dry DMSO (100 mL) was stirred under a nitrogen atmosphere at 75° C. (bath temperature) for 95 h. The solution was then cooled and petroleum ether (500 mL) was added. After 15 min stirring at room temperature the layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated a further two times and then water (500 mL) was added to the resultant DMSO layer and the mixture was stirred at room temperature for 1 h to precipitate a yellow/orange solid that was collected by filtration and washed with water (5×100 mL), before being dried under vacuum and then washed with petroleum ether (2×100 mL). The yellowish orange solid was then stirred with warm acetone (1 L) for ca. 3 h before water (1 L) was added to precipitate the required product. The solid was collected by filtration, washed with acetone/water (1:1, 5×80 mL) and dried in vacuo over silica-gel, to give pure N4-(3-bromo-4-fluorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (165) (14.8 g, 79%) as a yellow/orange solid, mp 181-184° C.; 1H NMR δ [(CD3)2SO] 9.69 (s, 1H), 8.75 (s, 1H), 8.37 (s, 1H), 8.26 (dd, J=6.4, 2.6 Hz, 1H), 7.91-7.83 (m, 1H), 7.42 (t, J=8.8 Hz, 1H), 7.33 (br d, J=8.6 Hz, 2H), 7.27 (t, J=6.3 Hz, 1H), 7.16 (s, 1H), 6.91-6.85 (m, 2H), 4.49 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C21H17BrFN5O: C, 55.52; H, 3.77; N, 15.42%. Found C, 55.75; H, 3.88; N, 15.44%.

Workup

  1. temperatureThe solution was then cooled
  2. stirringAfter 15 min stirring at room temperature the layers
  3. customto separate
  4. customthe petroleum ether layer was decanted
  5. additionwater (500 mL) was added to the resultant DMSO layer
  6. stirringthe mixture was stirred at room temperature for 1 h
  7. customto precipitate a yellow/orange solid
  8. filtrationthat was collected by filtration
  9. washwashed with water (5×100 mL)
  10. custombefore being dried under vacuum
  11. washwashed with petroleum ether (2×100 mL)
  12. stirringThe yellowish orange solid was then stirred with warm acetone (1 L) for ca. 3 h before water (1 L)
  13. additionwas added
  14. customto precipitate the required product
  15. filtrationThe solid was collected by filtration
  16. washwashed with acetone/water (1:1, 5×80 mL)
  17. customdried in vacuo over silica-gel

Sources & evidence

ORD record
ord-38f9008a48a04492afcd24b75eeb8ce7
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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