Sodium bis(trimethylsilyl)amide → N-(5-((3-(6-amino-2-methyl-4-pyrimidinyl)-2-pyrazinyl)amino)-2-chloro-3-pyridinyl)methanesulfonamide

HRID 1812295

反応式

HRID 1812295 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].F[C:25]1[C:26]([C:31]2[N:36]=[C:35]([CH3:37])[N:34]=[C:33]([NH2:38])[CH:32]=2)=[N:27][CH:28]=[CH:29][N:30]=1>C1COCC1>[NH2:38][C:33]1[N:34]=[C:35]([CH3:37])[N:36]=[C:31]([C:26]2[C:25]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:30][CH:29]=[CH:28][N:27]=2)[CH:32]=1

参加物

5

反応物 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 665998716-(3-Fluoro-2-pyrazinyl)-2-methyl-4-pyrimidinamineHCID 71480920N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide

生成物 1

HCID 59548384N-(5-((3-(6-amino-2-methyl-4-pyrimidinyl)-2-pyrazinyl)amino)-2-chloro-3-pyridinyl)methanesulfonamide収率 5.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (Example 330, Step 2) (0.091 g, 0.413 mmol) in THF (2.5 mL) at 0° C. was added NaHMDS (1.0 M solution in THF) (1.876 mL, 1.876 mmol). After the addition, the reaction mixture continued to stir at 0° C. under N2 for 30 min. 6-(3-fluoropyrazin-2-yl)-2-methylpyrimidin-4-amine (0.077 g, 0.375 mmol) was added into the reaction mixture. The reaction mixture continued to stir at 0° C. for 10 min and was then slowly warmed up to RT. After 1 hour, the reaction mixture was partitioned between pH 7 buffer (1M TRIS-HCl) and CH2Cl2. The aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by HPLC (10-90% CH3CN and H2O with 0.1% NH4OH, flow rate equal to about 5 mL/min). The fractions containing the desired product were concentrated under a vacuum. The material was further purified by chromatography through a silica gel column (4 g), eluting with a gradient of 0% to 10% MeOH in CH2Cl2, to provide N-(5-((3-(6-amino-2-methyl-4-pyrimidinyl)-2-pyrazinyl)amino)-2-chloro-3-pyridinyl)methanesulfonamide (0.0080 g, 0.020 mmol, 5.24% yield) as a yellow solid. m/z (ESI, +ve) 407.0 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 10.12 (s, 1H); 8.85 (s, 2H); 8.35 (s, 1H); 8.23-8.30 (m, 1H); 7.22 (s, 1H); 6.87 (br. s., 1H); 3.14 (s, 3H); 2.42 (s, 3H).

後処理

  1. additionAfter the addition
  2. stirringto stir at 0° C. for 10 min
  3. temperaturewas then slowly warmed up to RT
  4. waitAfter 1 hour
  5. customthe reaction mixture was partitioned between pH 7 buffer (1M TRIS-HCl) and CH2Cl2
  6. extractionThe aqueous layer was extracted with CH2Cl2 (3×)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by HPLC (10-90% CH3CN and H2O with 0.1% NH4OH, flow rate equal to about 5 mL/min)
  11. additionThe fractions containing the desired product
  12. concentrationwere concentrated under a vacuum
  13. customThe material was further purified by chromatography through a silica gel column (4 g)
  14. washeluting with a gradient of 0% to 10% MeOH in CH2Cl2

出典と根拠

ORDレコード
ord-49a11560774e48dda48c0881d0ca1a42
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

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