Trifluoroacetic acid → 6-((3R,4R)-3-amino-tetrahydropyran-4-ylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

HRID 1396336ノート

反応式

HRID 1396336 の反応式
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][O:14][CH2:13][C@@H:12]2[NH:17]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[N:27]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl>[NH2:17][C@@H:12]1[C@H:11]([NH:10][C:7]2[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 86689706tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-methylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

生成物 1

HCID 716268186-((3R,4R)-3-amino-tetrahydropyran-4-ylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide収率 28.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-methylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (60 mg, 83% pure, 0.112 mmol) was dissolved in dichloromethane (0.85 mL) and cooled to 0° C. Trifluoroacetic acid (0.35 mL, 4.49 mmol) was added drop-wise, then the mixture was warmed to room temperature. After 3 h, the mixture was concentrated in vacuo then water, sodium bicarbonate solution and ethyl acetate were added. The aqueous phase was extracted with ethyl acetate. Sodium chloride was added to the aqueous layer and it was further extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by chromatography (silica, 0-10% methanol in dichloromethane) gave 6-((3R,4R)-3-amino-tetrahydropyran-4-ylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (11 mg, 28%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.61 (s, 1H) 8.39 (br. s., 1H) 8.12 (s, 1H) 7.65 (br. s., 1H) 7.60 (t, J=7.7 Hz, 1H) 6.95 (d, J=7.2 Hz, 1H) 6.85 (d, J=7.6 Hz, 1H) 6.75 (d, J=8.3 Hz, 1H) 4.10 (br. s., 1H) 3.79-3.89 (m, 1H) 3.66-3.75 (m, 1H) 3.49-3.57 (m, 1H) 3.37-3.47 (m, 1H) 3.00-3.08 (m, 1H) 1.94-2.12 (m, 1H) 1.76-1.92 (m, 1H) 1.63-1.73 (m, 1H). MS (EI/CI) m/z: 344 [M+H].

後処理

  1. temperaturethe mixture was warmed to room temperature
  2. concentrationthe mixture was concentrated in vacuo
  3. additionwater, sodium bicarbonate solution and ethyl acetate were added
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. additionSodium chloride was added to the aqueous layer and it
  6. extractionwas further extracted with ethyl acetate
  7. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by chromatography (silica, 0-10% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-5a736a2fd8434d6eb56aee2a21236cea
出典データセット
uspto-grants-2014_12
特許番号
US08901124B2

反応ノート

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