2-Pyridinemethanamine → HCID 77843981, compound

HRID 2170140Notes

Reaction equation

HRID 2170140 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+](O[N:38]1N=[N:45][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N1C=CC=CC=1CN>C1COCC1>[C:11]1([C:8]2[CH:9]=[CH:10][N:6]3[C:7]=2[C:2]([NH:38][CH2:39][C:44]2[CH:43]=[CH:42][CH:41]=[CH:40][N:45]=2)=[N:3][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:5]3)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 195092-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178514760HCID 178514760, compound

Product 1

HCID 77843981HCID 77843981, compoundYield 21.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-(4-Hydroxy-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.150 g, 0.408 mmol) was dissolved in THF (10 mL) and BOP reagent (0.271 g, 0.612 mmol) and DIPEA (0.214 mL, 1.23 mmol) were added. The reaction mixture was stirred at room temperature for 30 min. Pyridin-2-ylmethanamine (0.0660 g, 0.612 mmol) in THF (3 mL) was added to the reaction mixture and the resulting mixture was stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure and water was added to the residue. The aqueous layer was extracted with ethyl acetate (25×2 mL). The organic layer was dried (with anhydrous sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 3% methanol in CH2Cl2) to afford 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.0400 g, 21.4%). LCMS Condition B-38: retention time 1.99 min, [M+1]=458.2. HPLC Condition B-32: retention time 7.75 min, Purity 98.90%. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.94 (d, J=4.4 Hz, 2H), 6.85 (d, J=2.8 Hz, 1H), 7.29 (dd, J=5.2 Hz, J=6.8 Hz, 1H), 7.42 (t, J=4.6 Hz, 1H), 7.46-7.50 (m, 2H), 7.52-7.56 (m, 2H), 7.60 (dd, J=2.0 Hz, J=6.8 Hz, 2H), 7.75 (s, 2H), 7.79 (dt, J=1.6 Hz, J=7.6 Hz, 1H), 7.96 (d, J=2.8 Hz, 1H), 8.39 (dd, J=0.8 Hz, J=1.6 Hz, 1H), 8.94 (t, J=2.0 Hz, 1H), 9.07 (d, J=2.4 Hz, 1H), 9.58 (d, J=2.0 Hz, 1H).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 14 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure and water
  3. additionwas added to the residue
  4. extractionThe aqueous layer was extracted with ethyl acetate (25×2 mL)
  5. dry with materialThe organic layer was dried (with anhydrous sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 3% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-54b17af096ee45c1a19b032727d3beca
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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