Triethylamine → [1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-yl)-1H pyrazol-4-yl]-[2-(thiophen-2-ylsulfanyl)-ethyl]-amine

HRID 2273209Notes

Reaction equation

Br[CH2:2][CH2:3][S:4][C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[CH3:10][O:11][C:12]1[CH:13]=[C:14]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][C:20]1[O:19][CH2:18][CH:17]([N:26]3[CH:30]=[C:29]([NH2:31])[CH:28]=[N:27]3)[CH2:16][C:15]2=1.C(N(CC)CC)C>C(#N)C>[CH3:10][O:11][C:12]1[CH:13]=[C:14]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][C:20]1[O:19][CH2:18][CH:17]([N:26]3[CH:30]=[C:29]([NH:31][CH2:2][CH2:3][S:4][C:5]4[S:6][CH:7]=[CH:8][CH:9]=4)[CH:28]=[N:27]3)[CH2:16][C:15]2=1

Participants

Conditions

Temperature: 80 °C

Procedure

2-(2-Bromo-ethylsulfanyl)-thiophene (317 mg, 0.13 mmol, 1.0 eq) is added at room temperature to a stirred solution of 1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-yl)-1H-pyrazol-4-ylamine (50 mg, 0.13 mmol, 1.0 eq) in acetonitrile (6 mL), followed by triethylamine (19 μL, 0.13 mmol, 1.0 eq). After 72 hours stirring at 80° C., the reaction mixture is concentrated to give a residue that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:3:0 to 0:1:0 to 0:9:1, v/v/v) to afford [1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-yl)-1H-pyrazol-4-yl]-[2-(thiophen-2-ylsulfanyl)-ethyl]-amine as a brown viscous oil (9 mg, 14% yield).

Workup

concentrationthe reaction mixture is concentrated
customto give a residue that
customis purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:3:0 to 0:1:0 to 0:9:1, v/v/v)

Sources & evidence

ORD record: ord-e7f2852c327e4524bcb183f01b97a700
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120822B2

Reaction notes

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