Toluene → HCID 52935026、化合物

HRID 628955

反応式

HRID 628955 の反応式
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[C@H:7]([NH:15][C:16](=[O:21])[O:17][CH:18]([CH3:20])[CH3:19])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2].[CH3:23][O:24][CH2:25][CH2:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:30]3[CH:29]=[N:28][N:27]([CH2:26][CH2:25][O:24][CH3:23])[CH:31]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:15][C:16](=[O:21])[O:17][CH:18]([CH3:20])[CH3:19])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2]

参加物

7

反応物 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 112304911-(2-Methoxyethyl)-1H-pyrazole-4-boronic acid, pinacol esterHCID 52935020HCID 52935020、化合物2 回

生成物 1

HCID 52935026HCID 52935026、化合物

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒

実験手順

1-Methylethyl [(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for preparation see Intermediate 1) (185 mg), 1-[2-(methyloxy)ethyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (for a preparation see Journal of Heterocyclic Chemistry, 41(6), 931-939; 2004) (151 mg), potassium carbonate (90 mg) and tetrakis(triphenylphosphine)palladium(0) (28.9 mg) were combined in ethanol and toluene under nitrogen and heated to 80° C. for 18 h. The reaction was concentrated, the residue partioned between ethyl acetate (10 ml) and water (10 ml) and the aqueous layer was extracted with ethyl acetate (10 ml). The combined organics were washed with brine (25 ml), dried with sodium sulphate, filtered and concentrated. The residue was purified by MDAP (formate ×2) and the collected product dissolved in 1,4-dioxane (0.5 ml) and cooled in a CO2 bath then left on a freeze dryer overnight. The resulting white solid was dried at 40° C. under vacuum overnight to give 1-methylethyl ((2S,4R)-1-acetyl-2-methyl-6-{1-[2-(methyloxy)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (84.7 mg). LCMS (formate), Rt 0.84 min, MH+ 415

後処理

  1. concentrationThe reaction was concentrated
  2. extractionthe residue partioned between ethyl acetate (10 ml) and water (10 ml) and the aqueous layer was extracted with ethyl acetate (10 ml)
  3. washThe combined organics were washed with brine (25 ml)
  4. dry with materialdried with sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by MDAP (formate ×2)
  8. dissolutionthe collected product dissolved in 1,4-dioxane (0.5 ml)
  9. temperaturecooled in a CO2 bath
  10. customThe resulting white solid was dried at 40° C. under vacuum overnight

出典と根拠

ORDレコード
ord-9ad27da81bac46b78e4f45c19a0da560
出典データセット
uspto-grants-2016_04
特許番号
US09315487B2

関連ノート

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