Tetrahydrofuran → isobutyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 2079431Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2079431
[NH2:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[N:11]=[C:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[OH:25])[N:9]=2)[CH2:4]1.C1COCC1.C(N(CC)CC)C.Cl[C:39]([O:41][CH2:42][CH:43]([CH3:45])[CH3:44])=[O:40]>C(Cl)Cl>[OH:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:10]1[N:9]=[C:8]([N:5]2[CH2:6][CH2:7][C@@H:3]([CH2:2][NH:1][C:39](=[O:40])[O:41][CH2:42][CH:43]([CH3:45])[CH3:44])[CH2:4]2)[C:17]2[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=2)[N:11]=1

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 1361213492-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

Produkt 1

HCID 136121450isobutyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamateAusbeute 70,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A mixture of 2-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (200 mg, 0.6 mmol), THF (6.0 mL), and CH2Cl2 was stirred under an N2 atmosphere. Triethylamine (0.166 mL, 1.2 mmol) was added, and the reaction was cooled in an ice bath. To this was added 1 M isobutyl chloroformate solution (78 μL in 600 μL THF, 0.6 mmol). After allowing the reaction mixture to warm to room temperature, CH2Cl2 was added, and the organic solution washed twice with water, then dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in CH2Cl2/hexanes (1:1) gave isobutyl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate (183 mg, 70%). LC/MS: m/z 435.5 (M+H)+ at 2.63 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). LC/MS: m/z 435 (M+H)+ at 2.63 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J=8.2, 1.8 Hz, 1H), 8.22 (d, J=8.7 Hz, 1H), 7.58 (s, 1H), 7.42-7.31 (m, 3H), 6.93-6.89 (m, 2H), 4.17-3.91 (m, 3H), 3.80-3.69 (m, 3H), 3.34-3.30 (m, 1H), 3.21-3.07 (m, 2H), 2.49 (s, 3H), 2.16-2.08 (m, 1H), 1.88-1.74 (m, 2H), 0.88 (d, J=6.7 Hz, 6H) ppm.

Aufarbeitung

  1. temperaturethe reaction was cooled in an ice bath
  2. washthe organic solution washed twice with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-8794f0607e8349dfaad00c1455715f7c
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07928107B2

Notizen zur Reaktion

Wird geladen…