Reaktion #1780202

Reaktionsgleichung

triethylamine

(R)-2-(4-(3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

isobutyl chloroformate

→

(R)-isobutyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

Ausbeute 58.2%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   SonstigeThe mixture was quenched with H2O
3. 3
   Sonstigepartitioned between CH2Cl2 and H2O
4. 4
   Extraktionthe aqueous layer was extracted once more with CH2Cl2
5. 5
   TrocknenThe organic phase was dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Sonstigepurified via silica gel chromatography
8. 8
   workup.ADDITIONin a 1:1 mixture of hexanes and CH2Cl2

Vorschrift

Under an N2 atmosphere, triethylamine (0.35 mL, 2.5 mmol) was added to a solution of (R)-2-(4-(3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (0.40 g, 1.25 mmol) in DMF (6.0 mL). The reaction mixture was cooled to −20° C. external temperature, and isobutyl chloroformate (180 μL, 1.38 mmol) was added dropwise. The reaction was stirred for 10 minutes at −20° C. and 15 minutes at RT. The mixture was quenched with H2O, and partitioned between CH2Cl2 and H2O, and the aqueous layer was extracted once more with CH2Cl2. The organic phase was dried over Na2SO4, filtered and purified via silica gel chromatography using 6% EtOAc in a 1:1 mixture of hexanes and CH2Cl2 to yield (R)-isobutyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (compound 5) (306 mg, 58%). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (m, 1H), 8.18 (d, J=8.6 Hz, 1H), 7.59 (s, 2H), 7.35 (m, 2H), 6.92 (m, 2H), 4.06 (m, 5H), 3.75 (d, J=4.4 Hz, 2H), 2.49 (s, 3H), 2.23 (m, 1H), 2.03 (m, 1H), 1.83 (m, 1H), 0.87 (d, J=6.5 Hz, 6H) ppm. LC/MS: m/z 421.3 (M+H)+ at 2.54 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Quelle