(2-Methoxyethyl)(methyl)amine → 5-(1,3-Dioxan-2-yl)-N-(2-methoxyethyl)-N-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazol-3-amine

HRID 1038400ノート

反応式

HRID 1038400 の反応式
Cl[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[O:16][CH2:15][CH2:14][CH2:13][O:12]3)[CH:9]=2)[N:4]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[N:3]=1.[CH3:25][O:26][CH2:27][CH2:28][NH:29][CH3:30].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>C1COCC1>[O:12]1[CH2:13][CH2:14][CH2:15][O:16][CH:11]1[C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[N:3]=[C:2]2[N:29]([CH2:28][CH2:27][O:26][CH3:25])[CH3:30]

参加物

6

反応物 4

HCID 300977(2-Methoxyethyl)(methyl)amineHCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 584075883-Chloro-5-(1,3-dioxan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole

生成物 1

HCID 584076545-(1,3-Dioxan-2-yl)-N-(2-methoxyethyl)-N-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazol-3-amine収率 54%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a degassed solution of 400 mg (1.08 mmol) 3-chloro-5-(1,3-dioxan-2-yl)-1-{[2-(trimethylsilyl)-ethoxy]methyl}-1H-indazole (Example 45A) and 135 mg (1.52 mmol) 2-methoxy-N-methylethanamine in anhydrous THF (11 ml) were added under inert gas atmosphere 103 mg (0.22 mmol) 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl (XPhos), 50 mg (0.054 mmol) tris(di-benzylideneacetone)dipalladium(0) (Pd2dba3) and 5.42 ml (5.42 mmol) lithium hexamethyldisilazide solution (1 M in THF). The resulting mixture was stirred under reflux for 12 h. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was washed with water and with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 90:10 v/v) to yield the title compound as a white solid (246 mg, 42% of th.).

後処理

  1. temperatureunder reflux for 12 h
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was washed with water and with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 90:10 v/v)

出典と根拠

ORDレコード
ord-22ea54b2d24c4a57a6a9441ec226d804
出典データセット
uspto-grants-2013_10
特許番号
US08551989B2

反応ノート

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