Dimethylformamide → {1-[4-(2,4-Diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4'-methoxymethoxy-biphenyl-2-yloxymethyl]-cyclopropyl}-methanol

温度

60 °C

4-(2,4-Diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4′-methoxymethoxy-biphenyl-2-ol (2.5 g; 6.31 mmol) is dissolved in dimethylformamide (125 ml; dried over a molecular sieve) and potassium tert-butylate (920 mg; 8.2 mmol) is added at room temperature. A solution of [(1-bromomethyl-cyclopropyl)methoxymethyl]-benzene (2.253 g; 8.83 mmol) in dimethylformamide (3 ml) is then added and the mixture is stirred for 100 minutes at a bath temperature of 60° C. The reaction mixture is concentrated, diluted with water (100 ml) and extracted with methylene chloride (120 ml) and re-extracted (50 ml). The combined organic phases are concentrated and the residue is chromatographed over silica gel (300 g) with methylene chloride/methanol/NH4OH conc. (19/1/0.05). The combined pure fractions are concentrated and the residue is dissolved in acetic acid conc. (40 ml) and ethanol (10 ml) and hydrogenated over Pd/C 10% (900 mg). The reaction mixture is filtered with suction and the filtrate is concentrated. The residue is stirred with water (50 ml) and the pH is adjusted to approx. 10 by addition of NH4OH conc. The product which has precipitated out is filtered off with suction and the residue is washed with a little water and dried under a high vacuum. 2.24 g (95%) {1-[4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4′-methoxymethoxy-biphenyl-2-yloxymethyl]-cyclopropyl}-methanol are obtained as a colourless powder.

1. additionis added at room temperature
2. concentrationThe reaction mixture is concentrated
3. additiondiluted with water (100 ml)
4. extractionextracted with methylene chloride (120 ml)
5. extractionre-extracted (50 ml)
6. concentrationThe combined organic phases are concentrated
7. customthe residue is chromatographed over silica gel (300 g) with methylene chloride/methanol/NH4OH conc. (19/1/0.05)
8. concentrationThe combined pure fractions are concentrated
9. dissolutionthe residue is dissolved in acetic acid conc. (40 ml)
10. filtrationThe reaction mixture is filtered with suction
11. concentrationthe filtrate is concentrated
12. stirringThe residue is stirred with water (50 ml)
13. additionby addition of NH4OH conc. The product which
14. customhas precipitated out
15. filtrationis filtered off with suction
16. washthe residue is washed with a little water
17. customdried under a high vacuum

ORDレコード

ord-aa5d0cb9970442419bea1e4408a9f51e

出典データセット

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06821980B1