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

HRID 1877934Notes

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, 3 H), 2.69-2.82 (m, 1 H), 3.07-3.22 (m, 3 H), 4.02-4.22 (m, 2 H), 5.92-6.03 (m, 1 H), 7.27 (d, J=7.8 Hz, 1 H), 7.31 (s, 1 H), 7.36 (dd, J=7.8, 1.5 Hz, 1 H), 7.43 (d, J=1.3 Hz, 1 H), 8.68 (s, 1 H).

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-f2ec075e95d04fa5b068c6912dbb3e18
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314097B2

Reaction notes

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