Diisopropylethylamine → rac-[1-({[7-(Benzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl]carbonyl}amino)-2-methylpentan-2-yl]carbamic Acid tert-butyl Ester

HRID 1486306ノート

反応式

HRID 1486306 の反応式
[CH2:1]([O:8][C:9]1[N:14]2[N:15]=[C:16]([CH3:21])[C:17]([C:18]([OH:20])=O)=[C:13]2[CH:12]=[C:11]([CH3:22])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[C:54]([O:58][C:59](=[O:68])[NH:60][C:61]([CH2:66][NH2:67])([CH3:65])[CH2:62][CH2:63][CH3:64])([CH3:57])([CH3:56])[CH3:55]>O1CCCC1>[C:54]([O:58][C:59](=[O:68])[NH:60][C:61]([CH3:65])([CH2:62][CH2:63][CH3:64])[CH2:66][NH:67][C:18]([C:17]1[C:16]([CH3:21])=[N:15][N:14]2[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:10][C:11]([CH3:22])=[CH:12][C:13]=12)=[O:20])([CH3:57])([CH3:56])[CH3:55]

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 84723920rac-tert-Butyl (1-amino-2-methylpentan-2-yl)carbamateHCID 1178595217-Benzyloxy-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

生成物 1

HCID 117864691rac-[1-({[7-(Benzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl]carbonyl}amino)-2-methylpentan-2-yl]carbamic Acid tert-butyl Ester収率 65%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 240 mg (0.81 mmol) of 7-benzyloxy-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid (Example 139A) in 12 ml of tetrahydrofuran was admixed with 132 mg (0.97 mmol) of 1-hydroxy-7-azabenzotriazole and 186 mg (0.97 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The reaction mixture was stirred at room temperature for 10 minutes. The resulting mixture was admixed with 0.422 ml (2.43 mmol) of N,N-diisopropylethylamine and 210 mg (0.97 mmol) of rac-(1-aminomethyl-1-methylbutyl)carbamic acid tert-butyl ester from Example 152A. The mixture was stirred at room temperature for a further 18 hours, and the contents were then concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was removed and washed with water and aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography using a prepacked silica gel cartridge (mobile phase: cyclohexane/ethyl acetate, gradient 0% to 50%), which gave 370 mg (65% yield, 71% pure) of the target compound, which was used in the next step without further purification.

後処理

  1. stirringThe mixture was stirred at room temperature for a further 18 hours
  2. concentrationthe contents were then concentrated under reduced pressure
  3. customThe residue was partitioned between dichloromethane and water
  4. customThe organic phase was removed
  5. washwashed with water and aqueous sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography
  10. customgave 370 mg (65% yield, 71% pure) of the target compound, which
  11. customwas used in the next step without further purification

出典と根拠

ORDレコード
ord-0eee78bdd19c42ae83df06e459479b61
出典データセット
uspto-grants-2016_08
特許番号
US09422285B2

反応ノート

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