4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812308

Reaction equation

HRID 1812308 reaction equation
[Si:1]([O:8][CH2:9][C:10]([C:13]1[CH:14]=[C:15](B(O)O)[C:16]([F:19])=[N:17][CH:18]=1)([CH3:12])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[C:24]1[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([NH2:31])[N:25]=1.C([O-])(=O)C.[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[Si:1]([O:8][CH2:9][C:10]([C:13]1[CH:14]=[C:15]([C:24]2[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([NH2:31])[N:25]=2)[C:16]([F:19])=[N:17][CH:18]=1)([CH3:12])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 305914-Chloro-6-methyl-1,3,5-triazin-2-amineHCID 517044Potassium AcetateHCID 665999945-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acid

Product 1

HCID 666114554-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 34.5%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A yellow solution of 5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acid (177 mg, 0.541 mmol), 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9; 78 mg, 0.541 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.; 19.15 mg, 0.027 mmol), and potassium acetate (159 mg, 1.622 mmol) in a mixture of dioxane (4.0 mL) and water (1.0 mL) was stirred under argon at 100° C. for 2 h. The yellow reaction mixture was subsequently partitioned between CH2Cl2 (80 mL) and water (50 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic extracts were then dried over sodium sulfate and concentrated onto silica gel. Chromatographic purification (silica gel, 0 to 60% EtOAc/hexanes) provided 4-(5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (73.0 mg, 0.186 mmol, 34.5% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.56 (dd, J=9.2, 2.5 Hz, 1H), 8.33 (d, J=1.4 Hz, 1H), 5.65 (br. s., 2H), 3.57 (s, 2H), 2.54 (s, 3H), 1.37 (s, 6H), 0.84 (s, 9H), −0.03 (s, 6H). 19F NMR (377 MHz, CDCl3) δ −70.17 (d, J=9.2 Hz, 1 F). m/z (ESI, +ve) 392.3 (M+H)+.

Workup

  1. customThe yellow reaction mixture was subsequently partitioned between CH2Cl2 (80 mL) and water (50 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (2×30 mL)
  4. dry with materialThe combined organic extracts were then dried over sodium sulfate
  5. concentrationconcentrated onto silica gel
  6. customChromatographic purification (silica gel, 0 to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0e8a5956bbf1436c94d66708d419437d
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Linked notes

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