Lithium Hexamethyldisilazide → N'-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloro-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

HRID 1622029

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HRID 1622029 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH2:16])[N:10]=2)[C:5](F)=[N:6][CH:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([NH:25][S:26]([N:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])[C:21]([Cl:24])=[N:22][CH:23]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1.[NH4+].[Cl-]>[NH2:16][C:11]1[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([C:4]2[C:5]([NH:17][C:18]3[CH:19]=[C:20]([NH:25][S:26]([N:29]([CH3:31])[CH3:30])(=[O:27])=[O:28])[C:21]([Cl:24])=[N:22][CH:23]=3)=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:10]=1

참가 물질

6

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 666118184-(5-Chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 71480922N'-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

생성물 1

HCID 59548288N'-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloro-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide수율 68.5%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 25517Ammonium Chloride용매

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온도
0 °C

실험 절차

To a 100-mL round-bottomed flask was added 4-(5-chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 356, Step 1; 960 mg, 4.01 mmol), N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (1004 mg, 4.01 mmol) and lithium bis(trimethylsilyl)amide (Aldrich; 3352 mg, 20.03 mmol) in tetrahydrofuran (20 mL) at 0° C. After the addition, the reaction mixture was stirred at 0° C. for 20 min. The reaction mixture was diluted with satd NH4Cl (30 mL) and extracted with CH2Cl2 (3×200 mL). The organic extract was washed with satd NaCl (30 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography eluting with 5% MeOH/CH2Cl2 to give N′-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloro-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (1.29 g, 2.74 mmol, 68.5% yield) as a yellow solid. m/z (ESI, +ve ion) 470.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 2.61 (s, 3H) 2.95 (s, 6H) 5.48 (br. s., 2H) 6.80 (s, 1H) 8.31 (d, J=2.74 Hz, 1H) 8.38 (d, J=2.54 Hz, 1H) 8.74 (d, J=2.54 Hz, 1H) 8.85 (d, J=2.74 Hz, 1H) 12.35 (s, 1H).

후처리

  1. additionAfter the addition
  2. extractionextracted with CH2Cl2 (3×200 mL)
  3. extractionThe organic extract
  4. washwas washed with satd NaCl (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 5% MeOH/CH2Cl2

출처 및 근거

ORD 기록
ord-2bf44da04f8b49cb85554e3e473d890f
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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