Triethylamine → 3-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

To a stirred solution of 3-(2,5-dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate M) (1.16 g, 3.29 mmol) in NMP (32 ml) was added 3-Amino-1,1,1-trifluoro-2-methyl-propan-2-ol hydrochloride (commercially available) (591 mg, 3.29 mmol) followed by HATU (1.25 g, 3.29 mmol) and NEt3 (918 ul, 6.59 mmol) and the reaction mixture was left to stir at RT. After 1 h a further 0.2 equiv. NEt3 was added. After 15 min a further 0.4 equiv. NEt3 and 0.2 equiv. amine were added. After 30 min a further 0.1 equiv HATU was added. After 30 min most of the starting material had been consumed. The reaction mixture was added to EtOAc (50 ml), washed with 0.1M NaOH and the aqueous layer was back extracted with EtOAc (2×50 ml). The combined organic extracts were washed with water (2×150 ml), brine (100 ml), dried (MgSO4) and concentrated in vacuo to give the crude product as an orange oil.

1. waitthe reaction mixture was left
2. waitAfter 15 min a further 0.4 equiv
3. customAfter 30 min most of the starting material had been consumed
4. additionThe reaction mixture was added to EtOAc (50 ml)
5. washwashed with 0.1M NaOH
6. extractionthe aqueous layer was back extracted with EtOAc (2×50 ml)
7. washThe combined organic extracts were washed with water (2×150 ml), brine (100 ml)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo

ORD-Eintrag

ord-b52be2d77c364507b7cfdaae069bea8f

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09365552B2