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

HRID 347565Notes

Reaction equation

HRID 347565 reaction equation
[ClH:1].FC1C=CC=C(F)C=1[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[NH:21][C:22]([C:24]4C=NC=CC=4)=[CH:23][C:16]=23)=[C:10]([F:30])[CH:9]=1)=[O:6].Cl.FC1C=C([CH:64]([C:68]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([F:77])=[CH:73][CH:72]=2)=[O:69])C(N)=O)C=CC=1OC1C2=C(C)C(OCCN3CCOCC3)=CN2N=CN=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[ClH:1].[F:30][C:10]1[CH:9]=[C:8]([NH:7][C:5](=[O:6])[CH2:64][C:68]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([F:77])=[CH:73][CH:72]=2)=[O:69])[CH:13]=[CH:12][C:11]=1[O:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]2[NH:21][C:22]([CH3:24])=[CH:23][C:16]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131726240(3-Fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride salt2×HCID 1317262462,6-Difluoro-N-(3-fluoro-4-(2-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl)benzamide, hydrochloride salt2×

Product 1

HCID 131726247N1-(3-Fluoro-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride saltYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-2440153b1d4140a5b9883d48fbb45d8e
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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