Acetic Acid → 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-3-(ethylamino)-1H-indazole-1-carboxylic acid tert-butyl ester

HRID 218493

反応式

HRID 218493 の反応式
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]3[C:22]([C:23]#[N:24])=[C:21]([CH3:25])[NH:20][C:19]([CH3:26])=[C:18]3[C:27]#[N:28])=[CH:14][CH:15]=2)[C:10]([NH2:29])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:30](=O)[CH3:31].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]3[C:22]([C:23]#[N:24])=[C:21]([CH3:25])[NH:20][C:19]([CH3:26])=[C:18]3[C:27]#[N:28])=[CH:14][CH:15]=2)[C:10]([NH:29][CH2:30][CH3:31])=[N:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 24959832tert-Butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate

生成物 1

HCID 690460615-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-3-(ethylamino)-1H-indazole-1-carboxylic acid tert-butyl ester収率 76.6%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a stirred mixture of 13.40 g (25.74 mmol) 3-amino-5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-1H-indazole-1-carboxylic acid tert-butyl ester, from Synthetic Example 18, in 335 mL dry methanol, was added 2.19 mL acetaldehyde and 2.06 mL glacial acetic acid and the resulting mixture was stirred overnight at room temperature. The reaction was cooled (ice bath) before 3.24 g sodium cyanoborohydride was added in three portions. The mixture was stirred overnight at room temperature before the reaction was concentrated to roughly half volume under vacuum. The residue was partitioned between EtOAc and saturated aqueous sodium hydrogen carbonate solution and the organic extract washed with saturated aqueous sodium chloride solution and concentrated under vacuum. The residue was taken up in hot EtOAc and allowed to cool to room temperature before being triturated with diisopropyl ether. The stirred suspension was cooled (ice bath), filtered and the crude product washed with diisopropyl ether. The product was dried under vacuum to afford 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-3-(ethylamino)-1H-indazole-1-carboxylic acid tert-butyl ester (8.25 g, 76.6%) (Cpd. No. 117, Table 2). 1H-NMR (DMSO-D6, 300 MHz): δ=9.54 (br s, 1H), 7.86 (d, 1H), 7.73 (m, 1H), 7.41 (dd, 1H), 6.82 (t, 1H), 4.47 (s, 1H), 3.26-3.34 (partially obscured by solvent, m, 2H), 2.02 (s, 6H), 1.57 (s, 9H), 1.21 (t, 3H) ppm.

後処理

  1. additionwas added in three portions
  2. stirringThe mixture was stirred overnight at room temperature before the reaction
  3. concentrationwas concentrated to roughly half volume under vacuum
  4. customThe residue was partitioned between EtOAc and saturated aqueous sodium hydrogen carbonate solution
  5. extractionthe organic extract
  6. washwashed with saturated aqueous sodium chloride solution
  7. concentrationconcentrated under vacuum
  8. temperatureto cool to room temperature
  9. custombefore being triturated with diisopropyl ether
  10. temperatureThe stirred suspension was cooled (ice bath)
  11. filtrationfiltered
  12. washthe crude product washed with diisopropyl ether
  13. customThe product was dried under vacuum

出典と根拠

ORDレコード
ord-7abb3e5a388847569abde20d58d98ece
出典データセット
uspto-grants-2012_06
特許番号
US08198456B2

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