Pyridine → HCID 78323677, compound

HRID 2170144Notes

Reaction equation

HRID 2170144 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.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>C(Cl)Cl.O>[C:25]1([C:22]2[CH:23]=[CH:24][N:10]3[C:11]=2[C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[N:13][C:8]([C:4]2[CH:3]=[C:2]([NH:1][S:38]([CH3:37])(=[O:40])=[O:39])[CH:7]=[N:6][CH:5]=2)=[N:9]3)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 90386124HCID 90386124, compound

Product 1

HCID 78323677HCID 78323677, compoundYield 21.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2-(5-Aminopyridin-3-yl)-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (80.0 mg, 0.201 mmol) was dissolved in CH2Cl2 (10 mL) and pyridine (0.0500 mL, 0.610 mmol) was added, followed by methanesulfonyl chloride (26.0 mg, 0.221 mmol). The reaction mixture was stirred at room temperature for 3 h then diluted with water (10 mL) and the aqueous solution was extracted with CH2Cl2 (25×2 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-64 as described in general methods) to obtain N-(5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)methanesulfonamide (20.0 mg, 20.0%). LCMS Condition B-39: retention time 2.02 min, [M+1]=471.80. HPLC Condition B-32: retention time 6.96 min, Purity 99.40%. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.11 (s, 3H), 4.92 (d, J=4.8 Hz, 2H), 6.82 (d, J=2.8 Hz, 1H), 7.31 (dd, J=4.4 Hz, J=8.8 Hz, 2H), 7.46-7.61 (m, 8H), 7.79 (dt, J=2.0 Hz, J=7.6 Hz, 1H), 7.92 (d, J=2.8 Hz, 1H), 8.40 (d, J=4.0 Hz, 1H), 8.44 (t, J=2.4 Hz, 1H), 9.15 (d, J=2.0 Hz, 1H).

Workup

  1. extractionthe aqueous solution was extracted with CH2Cl2 (25×2 mL)
  2. dry with materialThe combined organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC (Condition B-64 as described in general methods)

Sources & evidence

ORD record
ord-47893886e2dc47cba1dda8e0c6f3f8e1
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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