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

HRID 1396354ノート

反応式

HRID 1396354 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[CH:16]=[CH:15][N:14]([CH3:17])[N:13]=2)[CH:3]=1.[NH2:18][C@@H:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]1[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29]>CN1CCCC1=O.C(OCC)(=O)C.O>[C:28]([O:27][C:26](=[O:32])[NH:25][C@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][C@H:19]1[NH:18][C:2]1[N:7]=[N:6][C:5]([C:8](=[O:9])[NH2:10])=[C:4]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH3:17])[N:13]=2)[CH:3]=1)([CH3:31])([CH3:29])[CH3:30]

参加物

6

反応物 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2 回HCID 866897226-chloro-4-(1-methyl-1H-pyrazol-3-ylamino)-pyridazine-3-carboxylic acid amide

生成物 1

HCID 86689723{(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrazol-3-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester収率 17.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒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-pyrazol-3-ylamino)-pyridazine-3-carboxylic acid amide (60 mg, 0.237 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (102 mg, 0.475 mmol) were dissolved in N-methylpyrrolidinone (1.5 mL). The reaction mixture was heated at 150° C. for 16 h, then additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (100 mg, 0.47 mmol total) was added in three portions over 6 d. The reaction mixture was cooled, diluted with ethyl acetate and water, and extracted with ethyl acetate. The combined organic extracts were washed with water and brine, and then dried (sodium sulfate), filtered, and concentrated in vacuo. The residue obtained was purified by chromatography (silica, 0 to 7% methanol in dichloromethane) to give {(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrazol-3-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (18 mg, 17%) as a brown amorphous residue. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 10.68-10.80 (m, 1H) 7.89-8.06 (m, 1H) 7.34-7.37 (m, 1H) 7.25 (d, J=2.3 Hz, 1H) 5.93 (d, J=2.3 Hz, 1H) 5.56-5.64 (m, 1H) 5.02-5.14 (m, 1H) 3.91-4.01 (m, 1H) 3.86 (s, 3H) 1.55 (br. s., 8H) 1.40 (s, 9H); LCMS (EI/CI) m/z: 431 [M+H].

後処理

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

出典と根拠

ORDレコード
ord-8366044f47cb484d863ceb11e1c358ea
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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