4-Methoxybenzylamine → N4-(3-chloro-4-(3-chlorobenzyloxy)phenyl)-N6-(4-methoxybenzyl)prido[3,4-d]pyrimidine-4,6-diamine

HRID 511784Notes

Reaction equation

HRID 511784 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[CH:27]=[C:26](F)[N:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=1.[CH3:29][O:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[CH:27]=[C:26]([NH:36][CH2:35][C:34]4[CH:37]=[CH:38][C:31]([O:30][CH3:29])=[CH:32][CH:33]=4)[N:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=1

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 68159039N-(3-chloro-4-(3-chlorobenzyloxy)phenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine

Product 1

HCID 131733271N4-(3-chloro-4-(3-chlorobenzyloxy)phenyl)-N6-(4-methoxybenzyl)prido[3,4-d]pyrimidine-4,6-diamine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
71.5 °C

Procedure

A mixture of compound 201 (2.60 g, 6.27 mmol) and 4-methoxybenzylamine (8.24 mL, 62.7 mmol) in dry DMSO (15 mL) was stirred under a nitrogen atmosphere at 71-72° C. (bath temperature) for 91 h. It was partitioned in between ethyl acetate (500 mL) and water (300 mL). The ethyl acetate layer was separated and washed further with water (3×300 mL); dried (MgSO4) and evaporated to give a crude product of N4-(3-chloro-4-(3-chlorobenzyloxy)phenyl)-N6-(4-methoxybenzyl)prido[3,4-d]pyrimidine-4,6-diamine (210). Chromatography on silica gel (ethyl acetate/petroleum ether=1:1) gave pure 210 (2.02 g, 61%) as a yellow/orange solid, mp 120-122° C.; 1H NMR δ [(CD3)2SO] 9.59 (s, 1H), 8.72 (s, 1H), 8.33 (s, 1H), 7.99 (d, J=2.4 Hz, 1H), 7.57-7.53 (m, 1H), 7.48-7.38 (m, 3H), 7.36-7.19 (m, 4H), 7.15 (br s, 1H), 6.91-6.85 (m, 2H), 5.25 (s, 1H), 4.48 (d, J=6.3 Hz, 2H, 3.71 (s, 3H). Anal. Calcd for C28H23Cl2N5O2: C, 63.16; H, 4.35; N, 13.15. Found C, 62.96; H, 4.63; N, 13.12.

Workup

  1. customIt was partitioned in between ethyl acetate (500 mL) and water (300 mL)
  2. customThe ethyl acetate layer was separated
  3. washwashed further with water (3×300 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated

Sources & evidence

ORD record
ord-11590ff9eae44221a8da7501b26a51f4
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Reaction notes

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