Benzylamine → HCID 78323676, compound

HRID 2170139Notes

Reaction equation

HRID 2170139 reaction equation
O[C:2]1[C:7]2=[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:9]=[CH:10][N:6]2[N:5]=[C:4]([C:17]2[CH:18]=[C:19]([S:23]([NH2:26])(=[O:25])=[O:24])[CH:20]=[N:21][CH:22]=2)[N:3]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:63]([NH2:70])[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>C1COCC1>[CH2:63]([NH:70][C:2]1[C:7]2=[C:8]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:9]=[CH:10][N:6]2[N:5]=[C:4]([C:17]2[CH:18]=[C:19]([S:23]([NH2:26])(=[O:24])=[O:25])[CH:20]=[N:21][CH:22]=2)[N:3]=1)[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178514760HCID 178514760, compound

Product 1

HCID 78323676HCID 78323676, compoundYield 20.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-(4-Hydroxy-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.100 g, 0.272 mmol) was dissolved in THF (10 mL) and BOP reagent (0.181 g, 0.408 mmol) and DIPEA (0.143 mL, 0.817 mmol) were added. The reaction mixture was stirred at room temperature for 30 min. Benzylamine (0.0440 g, 0.408 mmol) in THF (3 mL) was added and the reaction mixture was stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure and water was added (30 mL). The resulting aqueous solution was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep HPLC (Condition B-61 as described in general methods) to obtain 5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.0250 g, 20.1%). LCMS Condition B-38: retention time 2.08 min, [M+1]=457.2. HPLC Condition B-5: retention time 20.11 min, Purity 97.00%. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.84 (d, J=5.6 Hz, 2H), 6.76 (t, J=5.6 Hz, 1H), 6.84 (d, J=2.8 Hz, 1H), 7.30 (t, J=7.2 Hz, 1H), 7.34 (t, J=7.6 Hz, 2H), 7.40-7.45 (m, 3H), 7.48 (t, J=7.6 Hz, 2H), 7.55 (dd, J=1.6, J=3.4 Hz, 2H), 7.68 (br s, 2H), 7.95 (d, J=2.4 Hz, 1H), 8.94 (t, J=2.2 Hz, 1H), 9.05 (d, J=2.4 Hz, 1H), 9.53 (d, J=1.6 Hz, 1H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 14 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure and water
  3. additionwas added (30 mL)
  4. extractionThe resulting aqueous solution was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by prep HPLC (Condition B-61 as described in general methods)

Sources & evidence

ORD record
ord-e8d6fc1070934b36bc01a329bd24eea2
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

Loading…