Hydrochloric Acid → HCID 86651576, compound

Temperature

80 °C

A scintillation vial equipped with a magnetic stirrer was added (2S,3R)-ethyl 2-methylmorpholine-3-carboxylate (383 mg, 2.211 mmol), DMF (3 ml), 2,4-dichloropyrimidin-5-amine (363 mg, 2.211 mmol), followed by DIEA (0.386 ml, 2.211 mmol). The reaction was stirred at 80° C. for 16 hours. NaOH (2 mL, 2.5N) was added and continued heating at 110° C. for 2 hours. After cooling to room temperature Boc2O (2 eq.) was added and stirred for 16 hours. The reaction was acidified with HCl (6N) to pH of about 2. The reaction mixture was poured into ethyl acetate and washed successively with water, brine, then dried over Na2SO4, and concentrated in vacuo to give a crude oil. Crystals formed after standing for 16 hours. The crystals were filtered and washed with ether to afforded (6aR,7S)-2-chloro-7-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (128 mg, 0.503 mmol, 22.73% yield) as a brown solid. The mother liquor was treated with TFA to afforded a crude (2S,3R)-2-methylmorpholine-3-carboxylic acid, TFA (145 mg, 0.559 mmol, 25.3% yield) which was combined with 2,4-dichloropyrimidin-5-amine (164 mg, 1 mmol) in DMF (1 ml) and DIEA (0.524 ml, 3.00 mmol). The reaction was heated at 80° C. for 16 hours. The reaction solution was poured into ethyl acetate and successively washed with water and brine. The organic layer was dried over Na2SO4, concentrated in-vacuo to give a brown oil. The oily residue was allowed to stand for 16 hour to give a solid which was filtered and rinsed with ether to afford (6aR,7S)-2-chloro-7-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (77 mg, 0.302 mmol, 30.2% yield). MS [M+H] found 255.

1. customA scintillation vial equipped with a magnetic stirrer
2. temperaturecontinued heating at 110° C. for 2 hours
3. additionwas added
4. stirringstirred for 16 hours
5. washwashed successively with water, brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customto give a crude oil
9. customCrystals formed
10. waitafter standing for 16 hours
11. filtrationThe crystals were filtered
12. washwashed with ether

ORD record

ord-e0e8b4b9fe37492ebc01a500b344f0f9

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163755B2