Ammonia → (trans)-2-{4-[({4-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxamide

HATU (0.23 g, 0.60 mmol) and (+)-(trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxylic acid (III-3c) (0.20 g, 0.46 mmol) in DMF (15 mL) were stirred at RT for 10 min, then a solution of ammonia in MeOH (3 mL, 21 mmol) was added. The solution was stirred at RT for 16 h, then water (50 mL) and dichloromethane (50 mL) were added and the organic layer was separated, washed with water (50 mL), dried over Na2SO4, filtered and concentrated. The crude material was purified on silica gel eluting with an increasing gradient from 50% ethyl acetate/hexanes to 100% ethyl acetate to give the title compound as a white powder (0.095 g, 48%). 1H NMR (400 MHz, DMSO) δ 8.01 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.1 Hz, 2H), 7.46 (s, 1H), 6.82 (d, J=8.2 Hz, 2H), 6.78 (s, 1H), 6.51 (d, J=8.3 Hz, 2H), 6.20 (t, J=5.8 Hz, 1H), 4.38 (d, J=5.6 Hz, 2H), 2.42 (s, 3H), 2.04-1.99 (m, 1H), 1.63-1.59 (m, 1H), 1.18-1.14 (m, 1H), 1.01-0.97 (m, 1H). ES-MS m/z 433.2 (MH+).

1. customthe organic layer was separated
2. washwashed with water (50 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude material was purified on silica gel eluting with an increasing gradient from 50% ethyl acetate/hexanes to 100% ethyl acetate

ORD-Eintrag

ord-d2640cf31f7a45f189afb3e6b1ae9570

Quelldatensatz

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07834013B2