(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689795、化合物

HRID 1396459ノート

反応式

HRID 1396459 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:17]=[CH:16][CH:15]=[C:14]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[N:13]=2)[CH:3]=1.[NH2:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>CN1C(=O)CCC1>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[N:13]=1)(=[O:9])[NH2:10]

参加物

4

反応物 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2 回HCID 86689794HCID 86689794、化合物

生成物 1

HCID 86689795HCID 86689795、化合物収率 35.2%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

A resealable pressure tube was charged with 6-chloro-4-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxamide (200 mg, 631 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (135 mg, 631 μmol) in NMP (2.00 mL). The reaction mixture was heated in an oil bath with stirring at 120° C. for 18 h. Then added more tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (135 mg, 631 μmol) in small portions during 7 hours and reaction continued for 18 h. The solvent was distilled off under high vacuum. The residue was dissolved in dichloromethane containing few drops of methanol and then purified by flash column (spherical silica 20-45 μM, 50 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to yield tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (110 mg, 222 μmol, 35.2% yield) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 11.48 (s, 1H), 8.82 (br. s., 1H), 8.00-8.11 (m, 1H), 7.62 (t, J=7.9 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H), 6.79 (d, J=8.3 Hz, 1H), 5.53-5.85 (m, 2H), 5.06 (d, J=8.3 Hz, 1H), 4.47 (br. s., 1H), 3.80-3.99 (m, 1H), 1.24-1.93 (m, 23H); LC-MS 495.1 [M+H]+.

後処理

  1. temperatureThe reaction mixture was heated in an oil bath
  2. customreaction
  3. waitcontinued for 18 h
  4. distillationThe solvent was distilled off under high vacuum
  5. dissolutionThe residue was dissolved in dichloromethane containing few drops of methanol
  6. custompurified by flash column (spherical silica 20-45 μM, 50 g, Versaflash Supelco)
  7. washeluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2

出典と根拠

ORDレコード
ord-b8619cba9e1346ff8eccee29b7b035ba
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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