4-Pyridinemethanamine → (trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}-N-(4-pyridinylmethyl)cyclopropanecarboxamide TFA Salt

HATU (0.071 g, 0.18 mmol) and (+)-(trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxylic acid (III-3c) (0.062 g, 0.14 mmol) in DMF (5 mL) were stirred at RT for 45 min, then (4-pyridinylmethyl)amine (0.030 g, 0.28 mmol) was added. The solution was stirred at RT for 16 h, then saturated NaHCO3 solution (50 mL) and ethyl acetate (50 mL) were added. The organic layer was separated, washed with saturated NaHCO3 solution (50 mL), water (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated. The crude material was partially dissolved in dichloromethane (10 mL) and diethyl ether was added (10 mL). The solid was filtered, washed with diethyl ether, and dried to give the title compound as an orange residue. The solid was dissolved in CH2Cl2 (5 mL) and trifluoroacetic acid (1 mL) was added. The solution was concentrated to dryness to give the title compound as a TFA salt. 1H NMR (400 MHz, DMSO) δ 8.80 (t, J=5.9 Hz, 1H), 8.71 (d, J=5.7 Hz, 2H), 8.03 (d, J=8.4 Hz, 2H), 7.78 (d, J=8.3 Hz, 2H), 7.64 (d, J=5.9 Hz, 2H), 6.87 (d, J=8.3 Hz, 2H), 6.54 (d, J=8.2 Hz, 2H), 4.47 (bs, 2H), 4.41 (s, 2H), 2.43 (s, 3H), 2.15-2.10 (m, 1H), 1.81-1.77 (m, 1H), 1.28-1.23 (m, 1H), 1.14-1.09 (m, 1H).

1. customThe organic layer was separated
2. washwashed with saturated NaHCO3 solution (50 mL), water (50 mL), brine (50 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe crude material was partially dissolved in dichloromethane (10 mL)
7. additiondiethyl ether was added (10 mL)
8. filtrationThe solid was filtered
9. washwashed with diethyl ether
10. customdried

ORD-Eintrag

ord-9f7cc3de7ded4f2eab7bf9365aa101cc

Quelldatensatz

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07834013B2