4-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine → 2-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-methylpropan-1-ol

HRID 1812310Notes

Reaction equation

HRID 1812310 reaction equation
[Si]([O:8][CH2:9][C:10]([C:13]1[CH:14]=[C:15]([C:29]2[N:34]=[C:33]([CH3:35])[N:32]=[C:31]([NH2:36])[N:30]=2)[C:16]([NH:19][C:20]2[CH:21]=[N:22][C:23]([O:27][CH3:28])=[C:24]([F:26])[CH:25]=2)=[N:17][CH:18]=1)([CH3:12])[CH3:11])(C(C)(C)C)(C)C>C1COCC1>[NH2:36][C:31]1[N:32]=[C:33]([CH3:35])[N:34]=[C:29]([C:15]2[CH:14]=[C:13]([C:10]([CH3:12])([CH3:11])[CH2:9][OH:8])[CH:18]=[N:17][C:16]=2[NH:19][C:20]2[CH:21]=[N:22][C:23]([O:27][CH3:28])=[C:24]([F:26])[CH:25]=2)[N:30]=1

Participants

3

Reactant 1

HCID 666117214-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595483892-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-methylpropan-1-olYield 63.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Tetra(N-butyl)ammonium fluoride (1.0M in THF) (Fluka, St. Louis, Mo.; 0.432 mL, 0.432 mmol) was added to an orange solution of 4-(5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (88.8 mg, 0.173 mmol) in THF (2.0 mL) at 0° C., and the resulting mixture was stirred at 0° C. for 10 min, then at 25° C. for 3 h. The reaction mixture was subsequently concentrated onto silica gel and chromatographically purified (silica gel, 0 to 100% EtOAc/hexanes) to provide 2-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-methylpropan-1-ol (44.0 mg, 0.110 mmol, 63.7% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.87 (s, 1H), 8.81 (d, J=2.7 Hz, 1H), 8.37-8.43 (m, 3H), 7.86 (br. s., 1H), 7.72 (br. s., 1H), 4.75 (br. s., 1H), 3.93 (s, 3H), 3.43 (s, 2H), 2.44 (s, 3H), 1.27 (s, 6H). 19F NMR (377 MHz, d6-DMSO) δ −139.89 to −139.79 (m, 1 F). m/z (ESI, +ve) 400.3 (M+H)+.

Workup

  1. waitat 25° C. for 3 h
  2. concentrationThe reaction mixture was subsequently concentrated onto silica gel
  3. customchromatographically purified (silica gel, 0 to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8f3a184030254b0584773aaac044500d
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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