Dichloromethane → HCID 66926564, compound

Temperature

-78 °C

(R)-1-(6-Methoxy-quinazolin-2-ylmethyl)-pyrrolidine-3-carboxylic acid methyl ester (600.00 mg, 1.9911 mmol) was dissolved in Methylene chloride (20 mL, 300 mmol), and cooled to at −78° C. A solution of 1.0 M of Boron tribromide in Methylene chloride (11.947 mL, 11.947 mmol) was then added dropwise. The reaction mixture was then warmed up to 23° C. gradually and then heated at 50° C. for 3 hours. The reaction mixture was then cooled to −78° C., and cold MeOH (30 mL) was added. The mixture was then left standing for 15 hours at 23° C. Solvent was removed under vacuum, and the residue was treated with K2CO3 (sat) to pH˜9, and then adjusted to pH˜7.5. Extracted with DCM (100×2 mL). Organic layers were washed with water, brine and dried over Na2SO4. The crude product was purified via chromatography (SiO2, 40 g, 0-10% MeOH/DCM) to give a pure product (540 mg, 94%). 1H NMR (MeOD) δ ppm: 9.26 (s, 1H), 7.86 (d, J=9.0 Hz, 1H), 7.55 (dd, J=9.2, 2.6 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H), 4.00 (d, J=3.0 Hz, 2H), 3.67 (s, 3H), 3.04-3.18 (m, 2H), 2.86 (d, J=2.5 Hz, 2H), 2.66-2.77 (m, 1H), 2.10 (s, 2H). MS (ESI, M+1): 288.10.

1. temperatureThe reaction mixture was then warmed up to 23° C. gradually
2. temperatureheated at 50° C. for 3 hours
3. temperatureThe reaction mixture was then cooled to −78° C.
4. waitThe mixture was then left
5. customSolvent was removed under vacuum
6. additionthe residue was treated with K2CO3 (sat) to pH˜9
7. extractionExtracted with DCM (100×2 mL)
8. washOrganic layers were washed with water, brine
9. dry with materialdried over Na2SO4
10. customThe crude product was purified via chromatography (SiO2, 40 g, 0-10% MeOH/DCM)

ORD record

ord-9e8895720c164d4095650fa02612161a

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802659B2