Lithium Hexamethyldisilazide → Tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-ylcarbamate

HRID 1621673Notes

Reaction equation

HRID 1621673 reaction equation
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[N:39][CH:40]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][N:15]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:10]2[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]3[C:2]([NH:34][C:35]4[CH:36]=[CH:37][C:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])=[N:39][CH:40]=4)=[N:3][CH:4]=[CH:5][CH:6]=3)[N:9]=2)=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 22064440tert-butyl N-(5-aminopyridin-2-yl)carbamateHCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66611588Tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-ylcarbamateYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-(2-Fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.150 g, 0.337 mmol) and tert-butyl 5-aminopyridin-2-ylcarbamate (0.0841 g, 0.402 mmol) were dissolved in THF (3 mL). The mixture was cooled to 0° C. and LiHMDS (Acros) (1.4 mL, 1.4 mmol) was added slowly. The dark red mixture was stirred at 0° C. for 1 h. The reaction mixture was partitioned between saturated aqueous ammonium chloride (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (25 g, eluent: EtOAc in hexanes 0%-50%) to give tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-ylcarbamate (0.145 g, 68% yield) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 11.83 (s, 1H); 8.76-8.87 (m, 1H); 8.39-8.48 (m, 1H); 8.25-8.34 (m, 1H); 7.91-8.03 (m, 1H); 7.76-7.87 (m, 1H); 7.10-7.24 (m, 5H); 6.86 (t, J=7.09 Hz, 4H); 6.70-6.81 (m, 1H); 4.83 (br. s., 4H); 3.80 (d, J=5.70 Hz, 6H); 2.58 (s, 3H); 1.53 (s, 9H). m/z (ESI, +ve ion) 635.0 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous ammonium chloride (20 mL) and EtOAc (20 mL)
  2. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel column chromatography (25 g, eluent: EtOAc in hexanes 0%-50%)

Sources & evidence

ORD record
ord-671d4f11f7ed4948b01ccaf6b5e4b629
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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