Potassium Carbonate → 2-(5-aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 2170146Notes

Reaction equation

HRID 2170146 reaction equation
[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11](Cl)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([NH2:39])[CH:36]=[N:37][CH:38]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:39][C:35]1[CH:34]=[C:33]([C:11]2[N:10]=[C:9]([NH:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:14]3=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:16]=[CH:17][N:13]3[N:12]=2)[CH:38]=[N:37][CH:36]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 438110685-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamineHCID 90386076N-benzyl-2-chloro-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 903862502-(5-aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amineYield 8.53%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

N-Benzyl-2-chloro-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (0.200 g, 0.597 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (0.263 g, 1.20 mmol, commercial) were dissolved in dioxane (10 mL) and water (2 mL). To the above solution was added K2CO3 (0.248 g, 1.79 mmol) and the reaction mixture was degassed with nitrogen for 15 minutes then PdCl2(dppf)-CH2Cl2 (0.0490 g, 0.0600 mmol) was added. The resulting reaction mixture was degassed for 20 minutes and heated to reflux at 110° C. for 14 h. The reaction mixture was allowed to cool, concentrated under reduced pressure and diluted with CH2Cl2 (10 mL). The resulting solid was filtered through a CELITE® bed and the filtrate dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-62 as described in general methods) to afford 2-(5-aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (20.0 mg, 8.53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.81 (d, J=6.0 Hz, 2H), 5.46 (s, 2H), 6.54 (t, J=6.0 Hz, 1H), 6.78 (d, J=2.8 Hz, 1H), 7.26-7.54 (m, 10H), 7.75 (dd, J=2.0 Hz, J=2.8 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H), 8.01 (d, J=2.8 Hz, 1H), 8.58 (d, J=1.6 Hz, 1H). LCMS Condition B-47: retention time 2.20 min, [M+1]=393.2. HPLC Condition B-63: retention time 24.18 min, Purity 97.00%.

Workup

  1. customthe reaction mixture was degassed with nitrogen for 15 minutes
  2. customThe resulting reaction mixture
  3. customwas degassed for 20 minutes
  4. temperatureheated
  5. temperatureto cool
  6. concentrationconcentrated under reduced pressure
  7. additiondiluted with CH2Cl2 (10 mL)
  8. filtrationThe resulting solid was filtered through a CELITE® bed
  9. dry with materialthe filtrate dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by preparative HPLC (Condition B-62 as described in general methods)

Sources & evidence

ORD record
ord-b98969f5ec564b8cbda67a6b6124343f
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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