Diisopropylethylamine → N1-(3-Fluoro-4-(2-(2-morpholinoethylamino)pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

HRID 2237183Notes

Reaction equation

HRID 2237183 reaction equation
Cl.[NH2:2][C:3]1[CH:24]=[CH:23][C:6]([O:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH:9]=2)=[C:5]([F:25])[CH:4]=1.NC1N=CN=C(OC2C=CC(NC(NC(=O)CC3C=CC(F)=CC=3)=S)=CC=2F)C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.COC1C=CC(CNC2N=C(OC3C=CC(N[C:108](=[O:120])[CH2:109][C:110]([NH:112][C:113]4[CH:118]=[CH:117][C:116]([F:119])=[CH:115][CH:114]=4)=[O:111])=CC=3F)C=CN=2)=CC=1>CN(C=O)C>[F:25][C:5]1[CH:4]=[C:3]([NH:2][C:108](=[O:120])[CH2:109][C:110]([NH:112][C:113]2[CH:118]=[CH:117][C:116]([F:119])=[CH:115][CH:114]=2)=[O:111])[CH:24]=[CH:23][C:6]=1[O:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:9]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 115389121-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea2×HCID 59852883N1-(4-(2-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideHCID 602092614-(4-Amino-2-fluorophenoxy)-N-(2-morpholinoethyl)pyridin-2-amine, hydrochloride salt

Product 1

HCID 59852917N1-(3-Fluoro-4-(2-(2-morpholinoethylamino)pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamideYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared from a mixture of 4-(4-amino-2-fluorophenoxy)-N-(2-morpholinoethyl)pyridin-2-amine, hydrochloride salt (15 mg, 0.043 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (Compound B of Example 1, 10 mg, 0.052 mmol), TBTU (17 mg, 0.052 mmol), DIPEA (30 μL), and DMF (1 mL) using a similar procedure described for the preparation of Compound C of Example 1. The crude product was purified by preparative HPLC (Shimadzu S5 VP-ODS 20×100 mm). The product obtained from HPLC purification was treated with 1 M HCl and lyophilized to give the title compound (10 mg, 40%) as a white solid. 1H NMR (DMSO-d6) δ 10.37 (s, 1H), 10.05 (s, 1H), 9.90 (br s, 1H), 7.90 (d, 1H, J=6.1 Hz), 7.75 (d, 1H, J=13.2 Hz), 7.58-7.55 (m, 2H), 7.53-7.50 (m, 1H), 7.40 (d, 1H, J=8.8 Hz), 7.24 (t, 1H, J=8.8 Hz), 7.08-7.03 (m, 3H), 6.39 (d, 1H, J=6.1 Hz), 6.11 (s, 1H), 3.80-3.81 (m, 4H), 3.67-3.65 (m, 2H), 3.47 (br s, 2H), 3.20 (br s, 4H); MS(ESI+) m/z 512.12 (M+H)+.

Workup

  1. customThe crude product was purified by preparative HPLC (Shimadzu S5 VP-ODS 20×100 mm)
  2. customThe product obtained from HPLC purification
  3. additionwas treated with 1 M HCl

Sources & evidence

ORD record
ord-5b2cee5838f64677a0e65808de1a82ca
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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