HCID 178418676, compound → HCID 178519622, compound

HRID 625760Notes

Reaction equation

[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([I:17])=[CH:14][CH:15]=3)[N:10]=[C:9]([C:18]([O:20]CC)=O)[N:8]=2)=[N:2]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([Mg]Br)=[CH:26][CH:25]=1>C1COCC1>[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([I:17])=[CH:14][CH:15]=3)[N:10]=[C:9]([C:18]([C:27]3[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=3)=[O:20])[N:8]=2)=[N:2]1

Participants

Conditions

Temperature: -40 °C

Procedure

To a suspension of ethyl 4-(1H-pyrazol-3-ylamino)-7-iodoquinazoline-2-carboxylate (0.130 g, 0.31 mmol) in THF (5 mL) at −40° C. was added (4-fluorophenyl)magnesium bromide (1.0 M solution in THF, 0.797 mL, 0.79 mmol). The mixture was stirred at −40° C. for 5 h, quenched with 1.0 N HCl (2.0 mL), and concentrated under reduced pressure. The residue wad purified on preparative HPLC (Phenomenex phenylhexyl reverse phase column, eluted with gradient of solvent B=0.05% HOAc/CH3CN and solvent A=0.05% HOAc/H2O) to afford (4-(1H-pyrazol-3-ylamino)-7-iodoquinazolin-2-yl)(4-fluorophenyl)methanone as a yellow solid (0.050 g, 34%). 1H NMR (300 MHz, DMSO-d6) δ 6.72 (s, 1H), 7.35 (t, 2H), 7.64 (s, 1H), 8.00 (d, 1H), 8.08 (dd, 2H), 8.28 (s, 1H), 8.55 (d, 1H), 10.88 (s, 1H), 12.55 (s, 1H); LC-MS (ESI) m/z 460 (M+H)+.

Workup

customquenched with 1.0 N HCl (2.0 mL)
concentrationconcentrated under reduced pressure
customThe residue wad purified on preparative HPLC (Phenomenex phenylhexyl reverse phase column
washeluted with gradient of solvent B=0.05% HOAc/CH3CN and solvent A=0.05% HOAc/H2O)

Sources & evidence

ORD record: ord-f16071285e4a4a769e62e7685195ec03
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09308207B2

Reaction notes

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