Pyridine → HCID 58529921, compound

HRID 1972798Notes

Reaction equation

HRID 1972798 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:19]3[CH:20]=[CH:21][C:22]4[C:26]([CH:27]=3)=[N:25][N:24]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:23]=4)[CH:9]=[C:10]([C:11]3[CH:12]=[C:13]([CH2:17]O)[CH:14]=[CH:15][CH:16]=3)[N:6]2[N:5]=[CH:4][N:3]=1.O=S(Cl)[Cl:37].N1C=CC=CC=1>O1CCOCC1>[CH2:28]([N:24]1[CH:23]=[C:22]2[C:26]([CH:27]=[C:19]([C:8]3[CH:9]=[C:10]([C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][Cl:37])[CH:12]=4)[N:6]4[C:7]=3[C:2]([NH2:1])=[N:3][CH:4]=[N:5]4)[CH:20]=[CH:21]2)=[N:25]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 58529400HCID 58529400, compound

Product 1

HCID 58529921HCID 58529921, compoundYield 24.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

{3-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-methanol (254 mg, 0.57 mmol) was suspended in 2 mL of dioxane and SOCl2 (83 μL, 1:1 mmol) was added followed by the dropwise addition of pyridine (0.14 mL, 1.7 mmol). The mixture was stirred for 1.5 hours and carefully quenched by the addition of 2M aqueous Na2CO3. The mixture was diluted with water and extracted with 3×10 mL of 10% MeOH/EtoAc. The combined organic fractions were washed with 1M aqueous H3PO4, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by ISCO® Redi-sep 12, 80% to 100% EtOAc/hexanes to provide 65 mg (24%) of the title compound as a crusty solid. 1H-NMR (DMSO-d6) 8.55 (s, 1H), 8.19 (s, 1H), 8.08, (d, 1H) 7.99 (s, 1H) 7.83 (d, 1H) 7.70 (s, 1H), 7.46 (t, 1H), 7.40 (t, 1H), 7.38-7.26 (m, 4H), 7.24 (d, 1H), 7.22 (s, 1H), 5.72 (s, 2H), 4.60 (s, 2H); LC-MS [M+H]+=465.3, 467.2, RT=3.24 min.

Workup

  1. customcarefully quenched by the addition of 2M aqueous Na2CO3
  2. additionThe mixture was diluted with water
  3. extractionextracted with 3×10 mL of 10% MeOH/EtoAc
  4. washThe combined organic fractions were washed with 1M aqueous H3PO4, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by ISCO® Redi-sep 12, 80% to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-c24f54c2cf8c4d8eb40df848822e1eb3
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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