Toluene → HCID 19919606, compound

HRID 1648363Notes

Reaction equation

HRID 1648363 reaction equation
C(O[C:4]([C:6]1[S:10][C:9]2[CH:11]=[CH:12][CH:13]=[C:14]([N:15]3[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=4)[CH2:17][CH2:16]3)[C:8]=2[CH:7]=1)=O)C.[Cl-].[NH4+:31].C[Al](C)C.C1(C)C=CC=CC=1>>[ClH:29].[Cl:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][CH2:21][N:18]2[CH2:19][CH2:20][N:15]([C:14]3[C:8]4[CH:7]=[C:6]([C:4]#[N:31])[S:10][C:9]=4[CH:11]=[CH:12][CH:13]=3)[CH2:16][CH2:17]2)=[CH:28][CH:27]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 15289966HCID 15289966, compoundHCID 16682925Trimethylaluminum

Product 1

HCID 19919606HCID 19919606, compoundYield 50%

Procedure

In an analogous manner to example 3, the title compound (0.39 g) as a white solid, mp 267°-269° C., is prepared from ethyl-4-[4-[2-(4-chlorophenyl)ethyl]-1-piperazinyl]-benzo[b]thiophene-2-carboxylate (1.60 g, 3.73 mmol, prepared in example 18), dry ammonium chloride (0.60 g, 11.2 mmol) and 2M trimethyl aluminum in toluene (5.6 mL, 11.2 mmol). The free base of the title compound is isolated by flash chromatography (ethyl acetate:hexane, 50:50, then ethyl acetate followed by ethanol:ethyl acetate, 50:50, Rf =0.4 in ethyl acetate:hexane, 40:60); 1H NMR (DMSO-d6) δ 11.35 (1H, bs), 8.50 (1H, s), 7.82 (1H, d, J=8.2 Hz), 7.57 (1H, t, J=8.0 Hz), 7.45 (2H, d, J=8.4 Hz), 7.36 (2H, d, J=8.4 Hz), 7.10 (1H, d, J=7.6 Hz), 3.63 (4H, m), 3.37 (6H, m), 3.17 (2H, m); 13C NMR (DMSO-d6) δ 148.02, 142.47, 136.12, 134.77, 131.45, 131.41, 130.58, 129.21, 128.58, 117.53, 114.72, 113.99, 107.10, 55.75, 51.10, 48.53, 28.61; IR (KBr) 2430, 2218, 1458, 958 cm-1 ; CI/MS (CH4) 382(100%). IC50 =13 nM (5HT1ABinding Affinity) IC50 =31 nM (5HT1DBinding Affinity) pA2 =7.37 (34%) (blocking of 5-HTl-like-mediated contraction in canine saphenous vein)

Sources & evidence

ORD record
ord-9d50eedfcfdc41c8b01f841d45eb57c3
Source dataset
uspto-grants-1995_07
Patent number
US05436246

Reaction notes

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