Diisobutylaluminumhydride → N-(7-(5-fluoro-4-(hydroxymethyl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468967

Reaktionsgleichung

Reaktionsgleichung von HRID 468967
[H-].C([Al+]CC(C)C)C(C)C.[CH:11]1([C:14]([NH:16][C:17]2[N:18]=[CH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[C:22]([C:27]2[C:36]([CH3:37])=[CH:35][C:30]([C:31](OC)=[O:32])=[C:29]([F:38])[CH:28]=2)[CH:21]=3)=[O:15])[CH2:13][CH2:12]1>C1COCC1>[F:38][C:29]1[C:30]([CH2:31][OH:32])=[CH:35][C:36]([CH3:37])=[C:27]([C:22]2[CH:21]=[C:20]3[C:25]([CH:26]=[C:17]([NH:16][C:14]([CH:11]4[CH2:13][CH2:12]4)=[O:15])[N:18]=[CH:19]3)=[CH:24][CH:23]=2)[CH:28]=1

Komponenten

4

Edukt 2

HCID 21225700DiisobutylaluminumhydrideHCID 67974657Methyl 4-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-2-fluoro-5-methylbenzoate

Produkt 1

HCID 67974756N-(7-(5-fluoro-4-(hydroxymethyl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamideAusbeute 57,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

Diisobutylaluminum hydride (1.0 mol/L) in THF (1.1 mL, 1.06 mmol) was added dropwise to a solution of methyl 4-[3-(cyclopropanecarbonylamino)-7-isoquinolyl]-2-fluoro-5-methyl-benzoate (100 mg, 0.26 mmol) in THF (1 mL) cooled at −15° C. The reaction mixture warmed to room temperature. After 1 hour, the reaction mixture was quenched with saturated aqueous ammonium chloride, diluted with ethyl acetate (50 mL) and washed with 1.0M citric acid solution in water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 minutes). Desired fractions were combined and evaporated in vacuo to afford the title compound as a white solid (52 mg, 56%). 1H NMR (400 MHz, DMSO) δ 10.90 (s, 1H), 9.17 (s, 1H), 8.49 (s, 1H), 8.02 (s, 1H), 7.92 (d, J=8.6 Hz, 1H), 7.69 (dd, J=8.5, 1.6 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 7.11 (d, J=10.7 Hz, 1H), 5.26 (s, 1H), 4.58 (s, 2H), 2.26 (s, 3H), 2.13-2.03 (m, 1H), 0.92-0.77 (m, 4H). LCMS (Method E): RT=4.595 min, M+H+=351.2.

Aufarbeitung

  1. temperatureThe reaction mixture warmed to room temperature
  2. customthe reaction mixture was quenched with saturated aqueous ammonium chloride
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed with 1.0M citric acid solution in water (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a residue that
  10. customwas purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 minutes)
  11. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-6a4993c777f4464cbf5471b39ceb7674
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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