Trifluoroacetic acid → 4-(5-(2-azidopropan-2-yl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812224Notes

Reaction equation

HRID 1812224 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[CH3:5][O:6][C:7]1[CH:48]=[CH:47][C:10]([CH2:11][N:12]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[C:13]2[N:18]=[C:17]([C:19]3[C:20]([NH:28][C:29]4[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=4)=[N:21][CH:22]=[C:23]([C:25]([CH3:27])=[CH2:26])[CH:24]=3)[N:16]=[C:15]([CH3:37])[N:14]=2)=[CH:9][CH:8]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>C(Cl)(Cl)Cl>[N:1]([C:25]([C:23]1[CH:24]=[C:19]([C:17]2[N:16]=[C:15]([CH3:37])[N:14]=[C:13]([N:12]([CH2:11][C:10]3[CH:9]=[CH:8][C:7]([O:6][CH3:5])=[CH:48][CH:47]=3)[CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[N:18]=2)[C:20]([NH:28][C:29]2[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=2)=[N:21][CH:22]=1)([CH3:27])[CH3:26])=[N+:2]=[N-:3]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 66612146HCID 66612146, compound

Product 1

HCID 866470644-(5-(2-azidopropan-2-yl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 100.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A slurry of sodium azide (0.075 g, 1.160 mmol) and N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(prop-1-en-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.171 g, 0.290 mmol) in CHCl3 (1 mL) at −15° C. was treated with a solution of trifluoroacetic acid (0.223 mL, 2.90 mmol) in CHCl3 (1 mL) added via syringe over 10 min. The cooling reaction mixture was allowed to gradually warm to room temperature and stirred overnight. The reaction was sealed and heated at 60° C. After 2 h, the reaction was poured onto ice and basified with 10 N NaOH. The reaction was partitioned between water and DCM. The aqueous layer was extracted with DCM (3×), and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give 4-(5-(2-azidopropan-2-yl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.184 g, 0.291 mmol, 100% yield). m/z (ESI, +ve ion) 633 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.67 (br. s., 1H); 8.90 (d, J=2.7 Hz, 1H); 8.38 (d, J=2.5 Hz, 1H); 8.26 (d, J=2.5 Hz, 1H); 7.91 (dd, J=8.8, 2.7 Hz, 1H); 7.18-7.26 (m, 4H); 6.81-6.94 (m, 4H); 6.73 (d, J=8.8 Hz, 1H); 4.90 (s, 2H); 4.81 (s, 2H); 3.94 (s, 3H); 3.82 (s, 3H); 3.78 (s, 3H); 2.59 (s, 3H); 1.64 (s, 6H).

Workup

  1. additionadded via syringe over 10 min
  2. customThe cooling reaction mixture
  3. customThe reaction was sealed
  4. temperatureheated at 60° C
  5. waitAfter 2 h
  6. customThe reaction was partitioned between water and DCM
  7. extractionThe aqueous layer was extracted with DCM (3×)
  8. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b2b11b301422414dbfb1842c10e71b28
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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