4-Methoxybenzylamine → HCID 86663608, compound

HRID 1520747Notes

Reaction equation

HRID 1520747 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([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:6]=[CH:7][CH:8]=1)#[CH:2].[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>[C:1]([C:3]1[CH:4]=[C:5]([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:6]=[CH:7][CH:8]=1)#[CH:2]

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 86663607HCID 86663607, compound

Product 1

HCID 86663608HCID 86663608, compoundYield 80.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of compound 164 (8.90 g, 33.7 mmol) and 4-methoxybenzylamine (44.2 mL, 337 mmol) in dry DMSO (80 mL) was stirred under nitrogen at 70° C. (bath temperature) for 158 h. The resultant solution was cooled briefly and then stirred with petroleum ether (2×400 mL) at room temperature for 15 min before the petroleum ether layer was decanted. Water (400 mL) was added to the DMSO layer and the mixture was stirred at room temperature for 3 h. The solid thus precipitated was collected by filtration and washed with water (5×100 mL), before being suctioned dry and then washed with petroleum ether (2×100 mL) and suctioned dry again. The resultant brownish orange solid was dissolved in warm acetone (400 mL) and water (500 mL) was added. The mixture was then stirred at room temperature for 1 h and the resultant solid was collected by filtration, washed with acetone/water (1:1, 5×80 mL) and dried in vacuo over silica-gel, to give N4-(3-ethynylphenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (167) (10.3 g, 80%) as a yellow/orange solid, mp 200-203° C.; 1H NMR δ [(CD3)2SO] 9.63 (s, 1H), 8.75 (s, 1H), 8.38 (s, 1H), 8.03 (br s, 1H), 7.94-7.88 (m, 1H), 7.41 (t, J=7.9 Hz, 1H), 7.34 (br d, J=8.6 Hz, 2H), 7.28-7.21 (m, 2H), 7.19 (s, 1H), 6.92-6.85 (m, 2H), 4.50 (d, J=6.3 Hz, 2H), 4.19 (s, 1H), 3.71 (s, 3H). Anal. Calcd for C23H19N5O: C, 72.42; H, 5.02; N, 18.36%. Found C, 72.28; H, 5.05; N, 18.22%.

Workup

  1. customwas decanted
  2. additionWater (400 mL) was added to the DMSO layer
  3. stirringthe mixture was stirred at room temperature for 3 h
  4. customThe solid thus precipitated
  5. filtrationwas collected by filtration
  6. washwashed with water (5×100 mL)
  7. custombefore being suctioned dry
  8. washwashed with petroleum ether (2×100 mL)
  9. customsuctioned dry again
  10. dissolutionThe resultant brownish orange solid was dissolved in warm acetone (400 mL)
  11. additionwater (500 mL) was added
  12. stirringThe mixture was then stirred at room temperature for 1 h
  13. filtrationthe resultant solid was collected by filtration
  14. washwashed with acetone/water (1:1, 5×80 mL)
  15. customdried in vacuo over silica-gel

Sources & evidence

ORD record
ord-376fdb4310314428965c4c85dc6eda40
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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