N,N'-Dimethylethylenediamine → 1,2,6',7'-Tetrahydro-2-oxo-1-(2,2,2-trifluoroethyl)spiro[3H-indole-3,5'-[5H]pyrrolo[1,2-c]imidazole]-6-carbonitrile

HRID 76889Notes

Reaction equation

[F:1][C:2]([F:25])([F:24])[CH2:3][NH:4][C:5]([C:7]1([C:15]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][C:16]=2Br)[N:11]2[CH:12]=[N:13][CH:14]=[C:10]2[CH2:9][CH2:8]1)=[O:6].CNCCNC.C([O-])([O-])=O.[Cs+].[Cs+]>[Cu]I.C1COCC1>[O:6]=[C:5]1[C:7]2([N:11]3[CH:12]=[N:13][CH:14]=[C:10]3[CH2:9][CH2:8]2)[C:15]2[C:20](=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=2)[N:4]1[CH2:3][C:2]([F:25])([F:24])[F:1]

Participants

Conditions

Temperature: 110 °C

Procedure

A suspension of 5-(2-Bromo-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid (2,2,2-trifluoroethyl)amide (0.168 g, 0.405 mmol), given in example 9, CuI (0.004 g, 0.021 mmol), N,N′-dimethylethylene diamine (0.005 mL, 0.042 mmol), Cs2CO3 (0.198 g, 0.609 mmol), and THF (15 mL) is heated to 110° C. for 60 h. The mixture is then filtered and concentrated. The residue is purified via flash chromatography (EtOAc/hexanes) to give 1,2,6′,7′-Tetrahydro-2-oxo-1-(2,2,2-trifluoroethyl)spiro[3H-indole-3,5′-[5H]pyrrolo[1,2-c]imidazole]-6-carbonitrile. MS (ESI) m/z 333.1 (M+H); NMR (400 MHz, CDCl3) δ ppm 2.85-2.96 (m, 1H), 3.03-3.18 (m, 2H), 3.27-3.39 (m, 1H), 4.20-4.34 (m, 1H), 4.43-4.57 (m, 1H), 6.86 (s, 1H), 7.04 (s, 1H), 7.30 (s, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.52 (dd, J=7.6, 1.3 Hz, 1H).

Workup

filtrationThe mixture is then filtered
concentrationconcentrated
customThe residue is purified via flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-21bc247718474bf19b83311a7ddd68af
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835646B2

Reaction notes

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