1-Chloro-4-(chloromethyl)benzene → HCID 118871741, compound

HRID 60360Notes

Reaction equation

[C:1]([O:4][CH2:5][CH2:6][CH2:7][N:8]1[C:13](=[O:14])[C:12]2[NH:15][C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:28])([F:27])[F:26])[CH:19]=3)=[CH:17][C:11]=2[N:10]([CH3:29])[C:9]1=[O:30])(=[O:3])[CH3:2].[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38]Cl)=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CC(=O)OCC.[Cl-].[Na+].O>[C:1]([O:4][CH2:5][CH2:6][CH2:7][N:8]1[C:13](=[O:14])[C:12]2[N:15]([CH2:38][C:35]3[CH:36]=[CH:37][C:32]([Cl:31])=[CH:33][CH:34]=3)[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:26])([F:27])[F:28])[CH:19]=3)=[CH:17][C:11]=2[N:10]([CH3:29])[C:9]1=[O:30])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of tert-butyl 3-(1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1H-pyrrolo[3,2-d]pyrimidin-3(2H,4H,5H)-yl)propyl acetate (See Intermediate 1, 60 mg, 0.141 mmol) in DMF (2 mL) was added 1-chloro-4-(chloromethyl)benzene (45.4 mg, 0.282 mmol), followed by K2CO3 (58.5 mg, 0.423 mmol). The reaction was heated at 85° C. for 18 h, cooled to RT then diluted with EA (10 mL) and brine (5 mL). The organic layer was washed with aq. 1N LiCl (3×20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography PE/EA (5:1 to 2:1) to give 3-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1H-pyrrolo[3,2-d]pyrimidin-3(2H,4H,5H)-yl)propyl acetate (30 mg, 38.7% yield) as a solid. LCMS: MH+ 550 and TR=2.078 min.

Workup

temperaturecooled to RT
washThe organic layer was washed with aq. 1N LiCl (3×20 mL)
dry with materialdried over Na2SO4
concentrationconcentrated to a residue which
customwas purified by chromatography PE/EA (5:1 to 2:1)

Sources & evidence

ORD record: ord-f6201b970e5645d0b10c38264603b4ce
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440983B2

Reaction notes

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