3-Fluorophenyl isocyanate → 1-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)urea

HRID 1621677Notes

Reaction equation

HRID 1621677 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[CH:39][C:6]([CH2:7][N:8]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:22][C:23]4[CH:24]=[CH:25][C:26]([NH2:29])=[N:27][CH:28]=4)=[N:18][CH:19]=[CH:20][CH:21]=3)[N:10]=2)=[CH:5][CH:4]=1.[F:41][C:42]1[CH:43]=[C:44]([N:48]=[C:49]=[O:50])[CH:45]=[CH:46][CH:47]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:22][C:23]4[CH:24]=[CH:25][C:26]([NH:29][C:49]([NH:48][C:44]5[CH:45]=[CH:46][CH:47]=[C:42]([F:41])[CH:43]=5)=[O:50])=[N:27][CH:28]=4)=[N:18][CH:19]=[CH:20][CH:21]=3)[N:10]=2)=[CH:39][CH:40]=1

Participants

4

Reactant 2

HCID 1230643-Fluorophenyl isocyanateHCID 66611800N5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-yl)pyridine-2,5-diamine

Product 1

HCID 666117991-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)ureaYield 35.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-yl)pyridine-2,5-diamine (Example 190, Step 4, 0.156 g, 0.293 mmol) and 3-fluorophenyl isocyanate (0.084 mL, 0.73 mmol) in THF (3 mL) was stirred at rt for 5 h. The resulting precipitate was collected to give 1-(5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)urea (0.0707 g) as a yellow solid. The filtrate and wash were concentrated and purified by silica gel chromatography (25 g, eluent: EtOAc in hexanes 0%-30%) to give a second batch of the product (0.1218 g). The combined yield was 0.1925 g (98%). 1H NMR (300 MHz, CDCl3) δ 11.77-11.96 (m, 2H); 8.80-8.93 (m, 1H); 8.43 (br. s., 1H); 8.32 (br. s., 1H); 7.93 (br. s., 1H); 7.45-7.63 (m, 2H); 7.27-7.35 (m, 2H); 7.15-7.24 (m, 4H); 6.66-6.95 (m, 7H); 4.85 (br. s., 4H); 3.79 (d, J=10.08 Hz, 6H); 2.62 (s, 3H). m/z (ESI, +ve ion) 672.0 (M+H)+.

Workup

  1. customThe resulting precipitate was collected

Sources & evidence

ORD record
ord-862490aac49d42ddb7bd3b1283a43b93
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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