Water → Ethyl 3-((5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)amino)-3-oxopropanoate

HRID 2170147Notes

Reaction equation

HRID 2170147 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:11]3=[C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:23]=[CH:24][N:10]3[N:9]=2)[CH:5]=[N:6][CH:7]=1.N1C=CC=CC=1.Cl[C:38](=[O:45])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41].O>C(Cl)Cl>[CH2:15]([NH:14][C:12]1[C:11]2=[C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:23]=[CH:24][N:10]2[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:38](=[O:45])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH:7]=[N:6][CH:5]=2)[N:13]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 118931Ethyl 3-chloro-3-oxopropionateHCID 903862502-(5-aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 90386195Ethyl 3-((5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)amino)-3-oxopropanoateYield 62.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(5-Aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (0.500 g, 1.27 mmol) was dissolved in CH2Cl2 (10 mL) and pyridine (0.103 mL, 1.27 mmol) was added, followed by the addition of ethyl 3-chloro-3-oxopropanoate (0.192 g, 1.27 mmol). The reaction mixture was stirred at room temperature for 14 h. Water (10 mL) was added to the reaction mixture followed by addition of CH2Cl2 (10×4 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using CombiFlash (REDISEP®, silica gel, 24 g, 3% methanol in CH2Cl2) to afford ethyl 3-((5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)amino)-3-oxopropanoate (0.400 g, 62.0%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (t, J=7.2 Hz, 3H), 3.54 (s, 2H), 4.15 (q, J=7.2 Hz, 2H), 4.82 (d, J=5.6 Hz, 2H), 6.66 (t, J=5.6 Hz, 1H), 6.81 (d, J=2.8 Hz, 1H), 7.27-7.55 (m, 10H), 7.91 (d, J=2.8 Hz, 1H), 8.81 (d, J=2.4 Hz, 1H), 8.87 (dd, J=2.4 Hz, J=1.6 Hz, 1H), 9.09 (d, J=1.6 Hz, 1H), 10.52 (s, 1H). LCMS Condition B-49: retention time 1.91 min, [M+1]=507.2. HPLC Condition B-32: retention time 10.36 min, Purity 98.80%.

Workup

  1. dry with materialThe combined organic extracts were dried over sodium sulfate
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-58489ad783464757adf01f240d4a1ad9
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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