Diisopropylethylamine → HCID 86634065, compound

Temperature

60 °C

Sulfur (1.2 g, 38 mmol) was added to Sodium tetrahydroborate (0.48 g, 13 mmol) in Tetrahydrofuran (20 mL). After 20 min, a solution of (3-Allyloxy-5-fluoro-4-nitro-phenyl)-dimethyl-amine (0.61 g, 2.5 mmol) in Tetrahydrofuran (20 mL) was added, and after 20 min the mixture was heated at 60° C. for an additional 2.5 h. The mixture was cooled, quenched with 100 mL satd. sodium bicarbonate and extracted with EtOAc (3×50 mL). The organic extract was washed with brine, dried over sodium sulfate and conc. in vacuo. The residue was dissolved in N-Methylpyrrolidinone (10 mL) and N,N-Diisopropylethylamine (0.65 mL, 3.7 mmol) and 2,4,5-Trichloro-pyrimidine (0.60 mL, 5.2 mmol) were added. The mixture was heated under an atmosphere of Nitrogen at 80° C. After 2 h, the solution was cooled, diluted with 100 mL Ether and washed with water (3×20 mL) and brine (50 mL). The aq. extract was back extracted with DCM (2×50 mL), which was then diluted with 100 mL ether and washed with water (50 mL) and brine (50 mL). The organic extracts were combined, dried over sodium sulfate and diluted with an equal volume of hexane before filtering through a 2″h×3″w circular pad of silica gel to remove baseline colored impurities. The filtrate was conc. and chromatographed (ISCO 80 g silica gel, 0-20% EtOAc:Hex), with the product eluting at 20%. Following conc., 2-Allyloxy-N(1)-(2,5-dichloro-pyrimidin-4-yl)-6-fluoro-N(4),N(4)-dimethyl-benzene-1,4-diamine was isolated as a green film (140 mg, 15% over two steps). 1H-NMR (CDCl3): 8.11 (s, 1H), 6.62 (s, 1H), 6.12 (d, 1H, J=13.1 Hz), 5.97 (s, 1H), 5.95 (m, 1H), 5.32 (d, 1H, J=17.2 Hz), 5.23 (d, 1H, J=9.4 Hz), 4.55 (m, 2H), 2.96 (s, 6H); 19F-NMR (CDCl3): −118.

1. temperatureThe mixture was cooled
2. customquenched with 100 mL
3. extractionsodium bicarbonate and extracted with EtOAc (3×50 mL)
4. extractionThe organic extract
5. washwas washed with brine
6. dry with materialdried over sodium sulfate and conc. in vacuo
7. dissolutionThe residue was dissolved in N-Methylpyrrolidinone (10 mL)
8. temperatureThe mixture was heated under an atmosphere of Nitrogen at 80° C
9. waitAfter 2 h
10. temperaturethe solution was cooled
11. washwashed with water (3×20 mL) and brine (50 mL)
12. extractionThe aq. extract
13. extractionwas back extracted with DCM (2×50 mL), which
14. additionwas then diluted with 100 mL ether
15. washwashed with water (50 mL) and brine (50 mL)
16. dry with materialdried over sodium sulfate
17. additiondiluted with an equal volume of hexane
18. filtrationbefore filtering through a 2″h×3″w circular pad of silica gel
19. customto remove baseline colored impurities
20. customchromatographed (ISCO 80 g silica gel, 0-20% EtOAc:Hex)
21. washwith the product eluting at 20%

ORD record

ord-5756b202fea840eba5207905fe4c2798

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148391B2