Ethanol → 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-ethoxybenzonitrile

HRID 76873Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[CH2:12][CH2:11]1)[C:5]#[N:6].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:70][CH2:71][OH:72]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].COCCOC>[CH:17]1[N:16]=[CH:15][N:14]2[CH:10]([C:9]3[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=3[O:72][CH2:71][CH3:70])[CH2:11][CH2:12][C:13]=12

Participants

Conditions

Temperature: 135 °C

Procedure

A solution of 3-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (0.090 g, 0.312 mmol) given in Example 3 (table 2), Pd2(dba)3 (0.029 g, 0.031 mmol), BINAP (0.039 g, 0.062 mmol), Cs2CO3 (0.204 g, 0.625 mmol), EtOH (0.091 mL, 1.54 mmol), and DME (4 mL) is heated in a microwave reactor at 135° C. for 1.5 h. At that point LCMS showed consumption of the starting material. The mixture is filtered and then the filtrate is concentrated. The residue is then purified by flash chromatography (0-10% MeOH/DCM) give 4-(6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-ethoxybenzonitrile. MS (ESI) m/z 254.1 (M+H); 1H NMR (400 MHz, MeOD) (TFA salt) δ ppm 1.32 (t, J=6.9 Hz, 3H), 2.69-2.82 (m, 1H), 3.07-3.22 (m, 3H), 4.02-4.22 (m, 2H), 5.92-6.03 (m, 1H), 7.27 (d, J=7.8 Hz, 1H), 7.31 (s, 1H), 7.36 (dd, J=7.8, 1.5 Hz, 1H), 7.43 (d, J=1.3 Hz, 1H), 8.68 (s, 1H).

Workup

customconsumption of the starting material
filtrationThe mixture is filtered
concentrationthe filtrate is concentrated
customThe residue is then purified by flash chromatography (0-10% MeOH/DCM)

Sources & evidence

ORD record: ord-25e1ecea06854028a6e26e4fd791b15b
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835646B2

Reaction notes

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