4-Methoxybenzylamine → N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

HRID 511794Notes

Reaction equation

HRID 511794 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25](F)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34][NH2:35])=[CH:32][CH:31]=1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25]([NH:35][CH2:34][C:33]4[CH:36]=[CH:37][C:30]([O:29][CH3:28])=[CH:31][CH:32]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 68158781N-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine

Product 1

HCID 86668931N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamineYield 77%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of compound 203 (3.07 g, 8.04 mmol) and 4-methoxybenzylamine (10.6 mL, 80.4 mmol) in dry DMSO (20 mL) was stirred under a nitrogen atmosphere at 70° C. (bath temperature) for 118 h. The mixture was then cooled and petroleum ether (200 mL) was added. It was stirred at room temperature for 15 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated with more petroleum ether (200 ml). Water (200 mL) was added and the mixture was stirred at room temperature overnight (22 h). It was filtered and washed solid with water (5×30 mL), then with petroleum ether (3×30 mL). The sticky yellow/orange solid was stirred with acetone (150 mL) at room temperature for 20 min. Water (150 mL) was added slowly and stirred further at room temperature for 45 min. The fine solid was collected by suction-filtration, washed with water/acetone (1:1) (4×20 mL), petroleum ether (3×20 mL) and dried in vacuum over silica-gel/KOH to give pure N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (212) (3.08 g, 77%) as a yellow/orange solid, mp 182-184° C.; 1HNMR δ [(CD3)2SO] 9.60 (s, 1H), 8.72 (s, 1H), 8.64-8.56 (m, 1H), 8.33 (s, 1H), 8.01 (d, J=2.6 Hz, 1H), 7.88 (td, J=7.7, 1.8 Hz, 1H), 7.71 (dd, J=9.0, 2.6 Hz, 1H), 7.58 (d, J=7.7 Hz), 7.42-7.19 (m, 5H), 7.15 (s, 1H), 6.93-6.84 (m, 2H), 5.25 (s, 2H), 4.48 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C27H23ClN6O2.0.6aCet011e: C, 64.80; H, 5.02; N, 15.74%. Found C, 64.47; H, 5.00; N, 15.95%.

Workup

  1. temperatureThe mixture was then cooled
  2. stirringIt was stirred at room temperature for 15 min
  3. customto separate
  4. customthe petroleum ether layer was decanted
  5. additionWater (200 mL) was added
  6. stirringthe mixture was stirred at room temperature overnight (22 h)
  7. filtrationIt was filtered
  8. washwashed solid with water (5×30 mL)
  9. stirringThe sticky yellow/orange solid was stirred with acetone (150 mL) at room temperature for 20 min
  10. additionWater (150 mL) was added slowly
  11. stirringstirred further at room temperature for 45 min
  12. filtrationThe fine solid was collected by suction-filtration
  13. washwashed with water/acetone (1:1) (4×20 mL), petroleum ether (3×20 mL)
  14. dry with materialdried in vacuum over silica-gel/KOH

Sources & evidence

ORD record
ord-9f69cdf1b66743edb7f580721852d40f
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Reaction notes

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