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 1621900

반응식

HRID 1621900 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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=9.2Hz, 1F). m/z (ESI, +ve) 392.3 (M+H)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-dba04e9b9cdd428f87e657aad6a1ea02
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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