Triphosgene → 5-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-one

HRID 510109Notes

Reaction equation

[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:15]=[C:16]([NH2:21])[C:17]([NH2:20])=[N:18][CH:19]=2)=[N:6]1.[C:26](=O)(OC(Cl)(Cl)Cl)[O:27]C(Cl)(Cl)Cl>N1C=CC=CC=1>[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:15]=[C:16]3[NH:21][C:26](=[O:27])[NH:20][C:17]3=[N:18][CH:19]=2)=[N:6]1

Participants

Conditions

Temperature: 100 °C

Procedure

40 mg (0.12 mmol) of the compound from example 52A were initially charged in pyridine (5.0 ml), then 39 mg (0.13 mmol) of bis(trichloromethyl) carbonate were added and the mixture was stirred at 100° C. for 1 h. The reaction mixture was concentrated, admixed with saturated aqueous sodium hydrogencarbonate solution and extracted twice with ethyl acetate. The collected organic phases were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient) and the product fractions were concentrated. This gave 9 mg (20% of theory) of the title compound in solid form.

Workup

concentrationThe reaction mixture was concentrated
extractionextracted twice with ethyl acetate
dry with materialThe collected organic phases were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated by rotary evaporation
customThe residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient)
concentrationthe product fractions were concentrated

Sources & evidence

ORD record: ord-ffaca47cec2d4465b5373fed01567249
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096592B2

Reaction notes

Loading…