2-chloro-N,N-dimethylacetamide → 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)-N,N-dimethylacetamide

A suspension of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene hydrochloride (310 mg, 0.72 mmol) in DCM (6 mL) and TEA (0.3 mL, 2.16 mmol) was sonicated and stirred before adding N,N-dimethyl-2-chloroacetamide (98 mg, 0.8 mmol) and TBAI (28 mg, 0.072 mmol) and the reaction mixture stirred for 72 h at RT before being concentrated in vacuo. The resultant residue was partitioned between water and DCM and the aqueous extracted five times with DCM, the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatpgraphy (SiO2, gradient 0 to 10% methanol in DCM) then triturated in diethyl ether to give 329 as a white solid (129 mg, 38%). LCMS: RT=2.71 min, [M+H]+=478. 1H NMR 400 MHz (CDCl3) δ: 8.44 (1 H, d, J=8.30 Hz), 7.61 (1 H, s), 7.04 (1 H, d, J=8.43 Hz), 6.91 (1 H, s), 5.91 (1 H, t, J=6.63 Hz), 4.45 (4H, d, J=14.92 Hz), 3.39 (2 H, m), 3.11 (2 H, m), 3.10 (3 H, s), 2.99 (1 H, m), 2.98 (3 H, s), 2.54 (2 H, m), 2.41 (3 H, s), 1.90 (4 H, s), 1.57 (6 H, d, J=6.65 Hz)

1. customwas sonicated
2. stirringthe reaction mixture stirred for 72 h at RT
3. concentrationbefore being concentrated in vacuo
4. customThe resultant residue was partitioned between water and DCM
5. extractionthe aqueous extracted five times with DCM
6. dry with materialthe combined organic extracts dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customthen triturated in diethyl ether

ORDレコード

ord-d602b0dbc93241ac9220c6d65a08d0e2

出典データセット

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08785626B2