Diisopropylethylamine → Ethyl 3-(3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenylamino)-3-oxopropanoate

HRID 347478Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([NH2:18])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[CH:15][CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1.C(N(C(C)C)CC)(C)C.Cl[C:29](=[O:36])[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:29](=[O:36])[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[CH:15][CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine (112 mg, 0.459 mmol, Compound C of Example 22) in methylene chloride (4 mL) at 0° C. was added 96 μL (0.55 mmol) of diisopropylethylamine followed by 61 μL (0.48 mmol) of ethyl 3-chloro-3-oxopropanoate. The reaction was stirred at 0° C. for 1 h and was then quenched with 10 mL of saturate NaHCO3 solution. The aqueous layer was extracted with chloroform (3×15 mL). The combined organic extracts were dried over anhydrous Na2SO4 and concentrated in vacuo to give the crude product as a yellow oil that solidified on standing (180 mg). 1H NMR (CDCl3) δ 9.45 (br s, 1H), 7.89 (s, 1H), 7.71 (dd, 1H, J=2.5, 1.5 Hz), 7.68 (dd, 1H, J=11.8, 2.2 Hz), 7.18 (m, 2H), 6.93 (dd, 1H, J=4.4, 1.4 Hz), 6.78 (dd, 1H, J=4.4, 2.6 Hz), 4.19 (q, 2H, J=7.2 Hz), 3.41 (s, 2H), 1.25 (t, 3H, J=7.2 Hz); MS(ESI+) m/z 359.1 (M+H)+.

Workup

customwas then quenched with 10 mL of saturate NaHCO3 solution
extractionThe aqueous layer was extracted with chloroform (3×15 mL)
dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-dcbad4b21f1c49718863bb967d5d0e16
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07173031B2

Reaction notes

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