(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)(4-hydroxypiperidin-1-YL)methanone → (5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanone

HRID 1621639Notes

Reaction equation

HRID 1621639 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C:32]([N:34]4[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36][CH2:35]4)=[O:33])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=CC=1>C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:17]=[C:18]([C:32]([N:34]3[CH2:35][CH2:36][CH:37]([OH:40])[CH2:38][CH2:39]3)=[O:33])[CH:19]=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=2)[N:10]=1

Participants

3

Reactant 1

HCID 66611784(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)(4-hydroxypiperidin-1-YL)methanone

Product 1

HCID 59548438(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanoneYield 56.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanone (0.109 g, 0.157 mmol) in TFA (7.0 mL) (Aldrich) was heated at 80° C. overnight. The solution was cooled to room temperature and concentrated to about 50% of the original volume under a stream of argon. A few pieces of ice were added, and then a saturated solution of NaHCO3 was added slowly until pH 7 was reached. The precipitate was isolated by filtration, and the filtercake was washed with water. The solid was suspended in 3 mL of MeOH and 1 mL of THF, then 0.5 mL of 1 N NaOH was added. The suspension was stirred at room temperature for 10 min. The solid was isolated by filtration and dried to give (5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanone (0.0406 g, 0.089 mmol, 56.9% yield) as an amorphous yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.08 (s, 1H); 8.85 (d, J=2.3 Hz, 1H); 8.41 (dd, J=4.8, 2.2 Hz, 2H); 8.35 (dd, J=12.6, 2.2 Hz, 1H); 7.96 (br. s., 1H); 7.81 (br. s., 1H); 4.79 (d, J=3.7 Hz, 1H); 3.95 (s, 3H); 3.74 (s, 3H); 3.20-3.27 (m, 2H); 2.44 (s, 3H); 1.76 (br. s., 2H); 1.40 (br. s., 2H). m/z (ESI, +ve ion) 455.0 (M+H)+.

Workup

  1. concentrationconcentrated to about 50% of the original volume under a stream of argon
  2. additionA few pieces of ice were added
  3. additiona saturated solution of NaHCO3 was added slowly until pH 7
  4. customThe precipitate was isolated by filtration
  5. washthe filtercake was washed with water
  6. addition1 mL of THF, then 0.5 mL of 1 N NaOH was added
  7. customThe solid was isolated by filtration
  8. customdried

Sources & evidence

ORD record
ord-99866f1a91d749e188d7027ec1afa0cf
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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