Cyclopropylboronic acid → HCID 57546246, Verbindung

HRID 913878

Reaktionsgleichung

Reaktionsgleichung von HRID 913878
Br[C:2]1[C:10]2[C:5](=[C:6]([CH:12]([O:14][CH2:15][C:16]3([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH3:13])[CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:3]=1.[CH:44]1(B(O)O)[CH2:46][CH2:45]1>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:11][C:8]1[CH:9]=[C:10]2[C:5](=[C:6]([CH:12]([O:14][CH2:15][C:16]3([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH3:13])[CH:7]=1)[N:4]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:3]=[C:2]2[CH:44]1[CH2:46][CH2:45]1

Komponenten

5

Edukt 2

HCID 2760897Cyclopropylboronic acidHCID 57546087(+/-)-tert-Butyl 4-((1-(3-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Produkt 1

HCID 57546246HCID 57546246, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(±)-tert-Butyl 4-((1-(3-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (100 mg, 0.14 mmol), cyclopropylboronic acid (18.5 mg, 0.22 mmol), and tetrakis(triphenylphosphine) palladium(0) (16.6 mg, 0.01 mmol) were combined in dry tetrahydrofuran (3 mL) in a microwave tube and sealed. The mixture was flushed with nitrogen then 0.5 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 100° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, washed with water (2×), then brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography on silica gel (15% ethyl acetate/hexanes) gave 65 mg (69%). 1H-NMR (CDCl3, 500 MHz) δ 7.58 (d, J=1.8 Hz, 1H), 7.21-7.23 (m, 2H), 6.97-7.01 (m, 3H), 5.50 (qAB, JAB=11.9 Hz, 2H), 5.00 (q, J=6.4 Hz, 1H), 3.69 (m, 2H), 3.33-3.45 (m, 2H), 3.19-3.27 (m, 2H), 3.01-3.06 (m, 2H), 2.01-2.14 (m, 3H), 1.79-1.89 (m, 2H), 1.43 (s, 9H), 1.41 (m, 3H), 0.96-1.01 (m, 4H), 0.67-0.83 (m, 2H), 0.09 (s, 9H). Mass spec.: 658.67 (MH)+.

Aufarbeitung

  1. customsealed
  2. customThe mixture was flushed with nitrogen
  3. addition0.5 mL of a 1 N potassium hydroxide aqueous solution was introduced
  4. temperatureAfter cooling to room temperature
  5. additionthe reaction mixture was diluted with ethyl acetate
  6. washwashed with water (2×)
  7. dry with materialbrine (2×), dried over sodium sulfate
  8. concentrationconcentrated
  9. customFlash chromatography on silica gel (15% ethyl acetate/hexanes) gave 65 mg (69%)

Quellen und Nachweise

ORD-Eintrag
ord-bd835bce783c48ac913b4d0b47edcd49
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026257B2

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