(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → {(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 1396368ノート

反応式

HRID 1396368 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[N:17]=[C:16]3[N:18]([CH3:21])[CH:19]=[CH:20][C:15]3=[CH:14][CH:13]=2)[CH:3]=1.[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33]>CN1CCCC1=O>[C:32]([O:31][C:30](=[O:36])[NH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:22][C:2]1[N:7]=[N:6][C:5]([C:8](=[O:9])[NH2:10])=[C:4]([NH:11][C:12]2[N:17]=[C:16]3[N:18]([CH3:21])[CH:19]=[CH:20][C:15]3=[CH:14][CH:13]=2)[CH:3]=1)([CH3:35])([CH3:33])[CH3:34]

参加物

4

反応物 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2 回HCID 86689730HCID 86689730、化合物

生成物 1

HCID 86689731{(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester収率 18%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
150 °C

実験手順

6-Chloro-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid amide (42 mg, 0.139 mmol), and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (89 mg, 0.416 mmol) were dissolved in N-methylpyrrolidinone (1.4 mL) and heated at 150° C. for 36 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (35 mg, 0.16 mmol) was added and the heating continued for 16 h more. The reaction mixture was cooled and concentrated in vacuo, then diluted with water, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. Purification by chromatography (silica, 0 to 5% methanol in dichloromethane) gave {(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (12 mg, 18%) as a light brown amorphous residue. LCMS (EI/CI) m/z: 481 [M+H].

後処理

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by chromatography (silica, 0 to 5% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-76448f7d08ca46adbe9ee60d46d18c40
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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