Lithium Hexamethyldisilazide → HCID 59548448, 화합물

HRID 1812194

반응식

HRID 1812194 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:31]1[C:36]([C:37]2[N:42]=[C:41]([CH3:43])[N:40]=[C:39]([NH2:44])[N:38]=2)=[CH:35][CH:34]=[CH:33][N:32]=1>C1COCC1>[NH2:44][C:39]1[N:40]=[C:41]([CH3:43])[N:42]=[C:37]([C:36]2[C:31]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][S:10]([C:13]4[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=4)(=[O:11])=[O:12])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:32][CH:33]=[CH:34][CH:35]=2)[N:38]=1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 665998524-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 71480919N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide

생성물 1

HCID 59548448HCID 59548448, 화합물수율 30.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

A solution of N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.124 g, 0.409 mmol) in THF (5 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (1.706 mL, 1.706 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 min. 4-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.070 g, 0.341 mmol) was added and the mixture was stirred at 0° C. for 10 min. The reaction mixture was then stirred at rt for 20 h. The reaction was quenched with sat. NH4Cl and the resulting mixture was partitioned between sat. NaHCO3 and CHCl3. The aqueous layer was extracted with CHCl3 (2×15 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by prep HPLC. Fractions containing the product were combined and concentrated. The residue was basified using sat. NaHCO3 (10 mL). The aqueous layer was extracted with CHCl3 (3×15 mL). The combined organic layers were dried over MgSO4 and concentrated to give the product as a yellow solid (0.050 g). m/z (ESI, +ve ion) 486.8 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 12.38 (s, 1H); 8.74-9.01 (m, 2H); 8.44 (d, J=3.22 Hz, 1H); 8.39 (d, J=2.34 Hz, 1H); 7.95 (dd, J=8.62, 5.12 Hz, 2H); 7.15 (t, J=8.48 Hz, 2H); 6.86-7.03 (m, 2H); 5.43 (br. s., 2H); 2.60 (s, 3H).

후처리

  1. stirringthe mixture was stirred at 0° C. for 10 min
  2. stirringThe reaction mixture was then stirred at rt for 20 h
  3. customThe reaction was quenched with sat. NH4Cl
  4. customthe resulting mixture was partitioned between sat. NaHCO3 and CHCl3
  5. extractionThe aqueous layer was extracted with CHCl3 (2×15 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by prep HPLC
  9. additionFractions containing the product
  10. concentrationconcentrated
  11. extractionThe aqueous layer was extracted with CHCl3 (3×15 mL)
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. concentrationconcentrated

출처 및 근거

ORD 기록
ord-4d888e19a8bb42f4ade7d40cf5be0646
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

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