Sodium bis(trimethylsilyl)amide → HCID 59548260、化合物

HRID 1621949

反応式

HRID 1621949 の反応式
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][C:5]([CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[C:26]([NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])[C:27]([Cl:30])=[N:28][CH:29]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[NH2:15][C:10]1[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]2[C:2]([NH:23][C:24]3[CH:25]=[C:26]([NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:33])=[O:34])[C:27]([Cl:30])=[N:28][CH:29]=3)=[N:3][CH:4]=[C:5]([CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH:6]=2)[N:9]=1

参加物

5

反応物 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 66611272HCID 66611272、化合物HCID 71480922N'-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

生成物 1

HCID 59548260HCID 59548260、化合物収率 44%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a stirred solution of 4-(2-fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 384, Step 2, 0.0614 g, 0.202 mmol) and N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (KY, 0.050 g, 0.199 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 0.80 mL, 0.80 mmol) was added dropwise at 0° C. The mixture was stirred at 0° C. for 45 min. The reaction mixture was partitioned between saturated aqueous ammonium chloride (30 mL) and 25% isopropanol in chloroform (20 mL). The aqueous phase was acidified to a pH of about 3 to 4 then extracted with 25% isopropanol in chloroform (2×30 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (25 g, eluent: iPrOH in CHCl3 0%-25%) to afford N′-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(4-morpholinylmethyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (0.0437 g, 44% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.28 (s, 1H) 9.57 (s, 1H) 8.82 (s, 1H) 8.76 (d, J=2.35 Hz, 1H) 8.53 (d, J=2.35 Hz, 1H) 8.29 (d, J=2.35 Hz, 1H) 7.74-7.98 (m, 2H) 3.57 (t, J=4.21 Hz, 4H) 3.48 (s, 2H) 2.79 (s, 6H) 2.46 (s, 3H) 2.35-2.43 (m, 4H). m/z (ESI, positive ion): 535.0 (M+H)+.

後処理

  1. customThe reaction mixture was partitioned between saturated aqueous ammonium chloride (30 mL) and 25% isopropanol in chloroform (20 mL)
  2. extractionthen extracted with 25% isopropanol in chloroform (2×30 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel column chromatography (25 g, eluent: iPrOH in CHCl3 0%-25%)

出典と根拠

ORDレコード
ord-a990192c019141538e32b86e6e7a372f
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

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