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

HRID 1812355

反応式

HRID 1812355 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([N:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.F[C:17]1[C:22]([C:23]2[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([NH2:30])[N:24]=2)=[CH:21][C:20]([O:31][CH3:32])=[CH:19][N:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH4+].[Cl-]>CN(C=O)C>[NH2:30][C:25]1[N:26]=[C:27]([CH3:29])[N:28]=[C:23]([C:22]2[C:17]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][S:10]([N:13]([CH3:15])[CH3:14])(=[O:11])=[O:12])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:18][CH:19]=[C:20]([O:31][CH3:32])[CH:21]=2)[N:24]=1

参加物

6

反応物 4

HCID 25517Ammonium Chloride2 回HCID 2724254Sodium bis(trimethylsilyl)amideHCID 666111694-(2-Fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 71480922N'-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

生成物 1

HCID 59548419N'-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-methoxy-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide収率 20.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (Example 384, Step 2, 0.0697 g, 0.278 mmol) and 4-(2-fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 330, Step 5, 0.0595 g, 0.253 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 1.02 mL, 1.02 mmol) was added dropwise at 0° C. The dark red solution was stirred at that temperature for 45 min. Sat'd NH4Cl (0.2 mL) was added to quench the reaction. The reaction mixture was poured into sat'd NH4Cl (20 mL) and the mixture was stirred for 5 min. The resulting brown precitipate was collected and the crude product was purified by preparative HPLC using a Phenomenex, Gemni 5 micron C18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The corresponding fractions were collected and concentrated in vacuo. The residue was collected and washed with water and small amount of MeOH to afford N′-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-methoxy-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (0.0240 g, 20% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.00 (br. s., 1H) 9.53 (br. s., 1H) 8.77 (br. s., 1H) 8.52 (br. s., 1H) 8.35-8.46 (m, 1H) 8.19 (br. s., 1H) 7.71-8.03 (m, 2H) 3.86 (br. s., 3H) 2.79 (br. s., 6H) 2.46 (br. s., 3H). m/z (ESI, positive ion) m/z: 466.0 (M+H)+.

後処理

  1. customto quench
  2. customthe reaction
  3. stirringthe mixture was stirred for 5 min
  4. customThe resulting brown precitipate was collected
  5. customthe crude product was purified by preparative HPLC
  6. customC18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  7. customThe corresponding fractions were collected
  8. concentrationconcentrated in vacuo
  9. customThe residue was collected
  10. washwashed with water and small amount of MeOH

出典と根拠

ORDレコード
ord-06a5dfc3700541dabdd606bcd0c907df
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

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