Methanol → N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(morpholinomethyl)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide

HRID 1812357

反応式

HRID 1812357 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]([CH3:35])(=[O:34])=[O:33])[C:27]([Cl:30])=[N:28][CH:29]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].CO>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]([CH3:35])(=[O:34])=[O:33])[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

6

反応物 4

HCID 887MethanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66611272HCID 66611272、化合物HCID 71480920N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide

生成物 1

HCID 59548408N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(morpholinomethyl)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide収率 77.3%

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 (0.0602 g, 0.198 mmol) and N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (Example 330, step 2, 0.0494 g, 0.223 mmol) in DMF (1 mL) in a 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 aq 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 to afford a brown residue. Upon addition of MeOH to the residue, a tan precipitate came out. The solid was collected via filtration and washed with MeOH to afford N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(morpholinomethyl)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide (0.0774 g, 77% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.26 (s, 1H) 9.66 (br. s., 1H) 8.76 (s, 1H) 8.67 (t, J=2.45 Hz, 2H) 8.31 (d, J=1.56 Hz, 1H) 7.74-8.01 (m, 2H) 3.43-3.66 (m, 6H) 3.14 (s, 3H) 2.38-2.48 (m, 7H). m/z (ESI, pos. ion): 505.9 (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. customto afford a brown residue
  7. filtrationThe solid was collected via filtration
  8. washwashed with MeOH

出典と根拠

ORDレコード
ord-e2052ad89d14417baf617337a0ba56e7
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

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