4-(5-(1-(Tert-butyldimethylsilyloxy)propan-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)propan-1-ol

HRID 1621909Notes

Reaction equation

HRID 1621909 reaction equation
[Si]([O:8][CH2:9][CH:10]([C:12]1[CH:13]=[C:14]([C:28]2[N:33]=[C:32]([CH3:34])[N:31]=[C:30]([NH2:35])[N:29]=2)[C:15]([NH:18][C:19]2[CH:20]=[N:21][C:22]([O:26][CH3:27])=[C:23]([F:25])[CH:24]=2)=[N:16][CH:17]=1)[CH3:11])(C(C)(C)C)(C)C>C1COCC1>[NH2:35][C:30]1[N:31]=[C:32]([CH3:34])[N:33]=[C:28]([C:14]2[CH:13]=[C:12]([CH:10]([CH3:11])[CH2:9][OH:8])[CH:17]=[N:16][C:15]=2[NH:18][C:19]2[CH:20]=[N:21][C:22]([O:26][CH3:27])=[C:23]([F:25])[CH:24]=2)[N:29]=1

Participants

3

Reactant 1

HCID 666113474-(5-(1-(Tert-butyldimethylsilyloxy)propan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595482852-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)propan-1-olYield 74.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Tetra(N-butyl)ammonium fluoride (1.0M in THF) (Fluka, St. Louis, Mo.; 1.206 mL, 1.206 mmol) was added to an orange solution of 4-(5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (241.0 mg, 0.482 mmol) in THF (5.0 mL) at 25° C., and the resulting mixture was stirred at 25° C. for 2 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)propan-1-ol (139.0 mg, 0.361 mmol, 74.8% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.88 (s, 1H), 8.66 (d, J=2.5 Hz, 1H), 8.41 (d, J=2.2 Hz, 1H), 8.35-8.40 (m, 1H), 8.25 (d, J=2.5 Hz, 1H), 7.88 (br. s., 1H), 7.74 (br. s., 1H), 4.70 (br. s., 1H), 3.93 (s, 3H), 3.49 (d, J=6.5 Hz, 2H), 2.83 (sxt, J=6.9 Hz, 1H), 2.44 (s, 3H), 1.22 (d, J=7.0 Hz, 3H). 19F NMR (376 MHz, d6-DMSO) δ −139.83 (d, J=13.0 Hz, 1F). m/z (ESI, +ve) 386.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated onto silica gel
  2. customchromatographically purified (silica gel, 0 to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3261e335972f4c65bfc52c3971eaa903
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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