Diisopropylethylamine → N1-(3-Fluoro-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride salt

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	2,6-Difluoro-N-(3-fluoro-4-(2-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl)benzamide, hydrochloride salt	HCID 131726246	—
Reactant	N1-(3-Fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride salt	HCID 131727132	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N1-(3-Fluoro-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride salt	HCID 131726247	34%

Reaction Steps

To a mixture of 3-fluoro-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzenamine (20 mg, 0.078 mmol, Compound E of Example 292), 3-(4-fluorophenylamino)-3-oxopropanoic acid (20 mg, 1 mmol, Compound A of Example 25), and HATU (44 mg, 0.12 mmol) in DMF (0.5 mL) was added DIPEA (0.1 mL). The reaction mixture was stirred at rt for 2 h and concentrated in vacuo. The residue was purified by preparative HPLC to give the desired product (HCl salt, 12.5 mg, 34%) as a white solid. 1H NMR (CD3OD) δ 8.05 (d, 1H, J=7.2 Hz), 7.79 (dd, 1H, J=12.7, 2.8 Hz), 7.50-7.53 (m, 2H), 7.27-7.36 (m, 2H), 6.97 (m, 2H), 6.70 (d, 1H, J=6.6 Hz), 6.20 (s, 1H), 3.47 (s, 2H), 2.40 (s, 3H); LC/MS(ESI+) m/z 437 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07439246B2
Source dataset	uspto-grants-2008_10
ORD ID	ord-d3a8ffbd09d54b8a82b8bce05f6a65f1
Source note	uspto-grants-2008_10