Water → HCID 90386174, compound

HRID 2170173Notes

Reaction equation

HRID 2170173 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][N: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][CH2:40][C:41]([O:43][CH3:44])=[O:42].O>C(Cl)Cl>[O:45]=[C:38]([NH:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N: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:3]=1)[CH2:39][CH2:40][C:41]([O:43][CH3:44])=[O:42]

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 90386124HCID 90386124, compound

Product 1

HCID 90386174HCID 90386174, compoundYield 65.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(5-Aminopyridin-3-yl)-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.200 g, 0.508 mmol, synthesized as described in Example 3) was dissolved in DCM (10 mL) and pyridine (0.0820 mL, 1.02 mmol) was added, followed by the addition of methyl 4-chloro-4-oxobutanoate (77.0 mg, 0.508 mmol). The reaction mixture was stirred at room temperature for 30 min. Water (10 mL) was added to the reaction mixture followed by addition of CH2Cl2 (4×10 mL). The combined organic extracts were separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford methyl 4-oxo-4-((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)amino)butanoate (0.170 g, 65.9%). 60 mg of the residue was further purified by preparative HPLC (Condition B-89 as described in general methods) to obtain methyl 4-oxo-4-(5-(5-phenyl-4-(pyridin-2-ylmethylamino) pyrrolo[1,2-f][1,2,4]triazin-2-yl)pyridin-3-ylamino)butanoate. LCMS Condition B-79: retention time 1.88 min, [M+1]=508.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.62-2.78 (m, 4H), 3.62 (s, 3H), 4.93 (s, 2H), 6.81 (d, J=2.4 Hz, 1H), 7.23-7.34 (m, 2H), 7.41-7.64 (m, 6H), 7.72-7.82 (m, 1H), 7.90-7.93 (m, 1H), 8.33-8.44 (m, 1H), 8.79-8.89 (m, 2H), 9.04-9.12 (m, 1H), 10.37 (s, 1H).

Workup

  1. customThe combined organic extracts were separated
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-df66a30933004485974123a42041b13a
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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