Hydrochloric Acid → HCID 78323978, compound

HRID 2170157Notes

Reaction equation

HRID 2170157 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]([C:24]2[CH:25]=[N:26][CH:27]=C([CH:31]=2)C#N)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:32].[K+].Cl.[O:35]1[CH2:40][CH2:39]OCC1>O>[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]([C:24]2[CH:25]=[N:26][CH:27]=[C:39]([CH:31]=2)[C:40]([OH:35])=[O:32])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 90386074HCID 90386074, compound

Product 1

HCID 78323978HCID 78323978, compoundYield 59.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

5-(4-(Benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinonitrile (prepared as in Example 11) (0.800 g, 1.99 mmol) was dissolved in dioxane (3 mL), and KOH (0.892 g, 15.9 mmol) was added. The reaction mixture was heated to 100° C. for 14 h. The reaction mixture was allowed to cool and concentrated under reduced pressure to remove dioxane. The residue obtained was diluted with water (10 mL) and neutralized with dilute HCl to pH 6. The solid was filtered and air dried. The solid was purified by preparative HPLC (Condition B-67 as described in general methods) to obtain 5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinic acid (0.500 g, 59.7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.83 (d, J=5.6 Hz, 2H), 6.66 (t, J=5.6 Hz, 1H), 6.83 (d, J=2.8 Hz, 1H), 7.26-7.56 (m, 10H), 7.96 (d, J=2.8 Hz, 1H), 8.99 (dd, J=1.6 Hz, J=2.0 Hz, 1H), 9.14 (d, J=2.0 Hz, 1H), 9.53 (d, J=1.6 Hz, 1H), 13.61 (br s, 1H). LCMS Condition B-44: retention time 1.54 min, [M+1]=422.2. HPLC Condition B-31: retention time 10.72 min, Purity 97.70%.

Workup

  1. temperatureto cool
  2. concentrationconcentrated under reduced pressure
  3. customto remove dioxane
  4. customThe residue obtained
  5. filtrationThe solid was filtered
  6. customair dried
  7. customThe solid was purified by preparative HPLC (Condition B-67 as described in general methods)

Sources & evidence

ORD record
ord-eb8ae04ca7a046549decd9e0ffb5adba
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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