4-Aminopyridine → HCID 67983712、化合物

HRID 1397167ノート

反応式

HRID 1397167 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CS([C:21]1[N:26]=[C:25]([C:27]2[C:28]([CH3:34])=[N:29][C:30]([NH2:33])=[N:31][CH:32]=2)[CH:24]=[CH:23][N:22]=1)=O>C1COCC1>[CH3:34][C:28]1[C:27]([C:25]2[CH:24]=[CH:23][N:22]=[C:21]([NH:1][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[N:26]=2)=[CH:32][N:31]=[C:30]([NH2:33])[N:29]=1

参加物

5

反応物 3

HCID 17274-AminopyridineHCID 2733832Lithium HexamethyldisilazideHCID 679833892-Methanesulfinyl-4'-methyl-[4,5']bipyrimidinyl-2'-ylamine

生成物 1

HCID 67983712HCID 67983712、化合物収率 1.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 4-aminopyridine (423 mg, 4.49 mmol) in THF (0.562 mL) cooled to −10° C. was added LHMDS (1M in THF) (1.123 mL, 1.123 mmol). The resulting suspension was warmed to rt and stirred for 15 minutes, after which time it was cooled back to −10° C. and 2-Methanesulfinyl-4′-methyl-[4,5′]bipyrimidinyl-2′-ylamine (20) (70 mg, 0.281 mmol) was then added. The reaction mixture was again warmed to rt and stirred for 1.5 hours. The reaction was quenched by slow addition of saturated ammonium chloride and the volatiles evaporated. The mixture was then diluted with DCM, the layers separated, and the organic layer washed with brine, dried with sodium sulfate, and concentrated. The crude residue was purified by flash column chromatography with a gradient of 2-20% MeOH in DCM. The product was further purified by reverse phase HPLC with a gradient of 10-90% MeCN in water over 15 minutes, to give the desired product as a white solid (1.39 mg, 0.44%). 1H NMR (400 MHz, MeOD) δ ppm 2.57 (s, 3 H) 7.13 (d, J=5.56 Hz, 1 H) 7.84 (d, J=6.57 Hz, 2 H) 8.30 (d, J=6.57 Hz, 2 H) 8.50 (s, 1 H) 8.57 (d, J=5.05 Hz, 1 H). HRMS (ES+) for C14 H13N7.H+ [MH+]: calcd, 280.1311. found, 280.1318. UV-LC: 100/100% UV purity at 214/254 nm; tR=2.93 minutes over 7.75 minutes.

後処理

  1. temperatureafter which time it was cooled back to −10° C.
  2. temperatureThe reaction mixture was again warmed to rt
  3. stirringstirred for 1.5 hours
  4. customThe reaction was quenched by slow addition of saturated ammonium chloride
  5. customthe volatiles evaporated
  6. additionThe mixture was then diluted with DCM
  7. customthe layers separated
  8. washthe organic layer washed with brine
  9. dry with materialdried with sodium sulfate
  10. concentrationconcentrated
  11. customThe crude residue was purified by flash column chromatography with a gradient of 2-20% MeOH in DCM
  12. customThe product was further purified by reverse phase HPLC with a gradient of 10-90% MeCN in water over 15 minutes

出典と根拠

ORDレコード
ord-ac9f32204a6142a48f31525dd4da3823
出典データセット
uspto-grants-2014_12
特許番号
US08901147B2

反応ノート

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