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 1621946

반응식

HRID 1621946 반응식
[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

참가 물질

6

반응물 4

HCID 25517Ammonium Chloride2회HCID 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

생성물 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-dimethylsulfamide수율 20.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-6eaa69be18d14010b526ba52fc47eaec
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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