Sulfuric Acid → HCID 86679707, compound

HRID 2367712Notes

Reaction equation

HRID 2367712 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]4[CH:22]=[N:23][CH:24]=[C:25]([CH2:27][N:28]5[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]5)[CH:26]=4)[CH:19]=3)[NH:14][N:13]=2)=[O:11])=[CH:5][CH:4]=1)#[N:2].S(=O)(=O)(O)[OH:35].[NH4+].[OH-]>C(O)(=O)C>[C:1]([C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]4[CH:22]=[N:23][CH:24]=[C:25]([CH2:27][N:28]5[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]5)[CH:26]=4)[CH:19]=3)[NH:14][N:13]=2)=[O:11])=[CH:5][CH:4]=1)(=[O:35])[NH2:2]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 86679708HCID 86679708, compound

Product 1

HCID 86679707HCID 86679707, compoundYield 93.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of N-(6-cyanopyridin-3-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazole-3-carboxamide (62) (200 mg, 0.45 mmol) in glacial acetic acid (2 mL) heated at 85° C. was carefully added dropwise sulfuric acid (2 mL). The reaction was heated at 85° C. for another 20 minutes before pouring into ice. The solution was basified with cold 5N NH4OH. The solids formed were filtered, washed with cold washed and dried under vacuum. The dry solid was suspended in DCM and a few drops of MeOH were added. The insoluble solids were filtered and discarded. The filtrate was concentrated and suspended again in DCM, boiled for 15 minutes and filtered. The solid was dried under vacuum to give N-(6-carbamoylpyridin-3-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-indazole-3-carboxamide (180) as a white solid (192 mg, 0.42 mmol, 93.7% yield). 1H NMR (DMSO-d6) δ ppm 1.36-1.42 (m, 2H), 1.48-1.55 (m, 4H), 2.38 (brs, 4H), 3.56 (s, 2H), 7.49 (s, 1H), 7.65 (d, J=9 Hz, 1H), 7.80 (d, J=9 Hz, 1H), 7.97 (s, 1H), 8.03 (s, 2H), 8.41 (s, 1H), 8.45 (d, J=2 Hz, 1H), 8.54 (dd, J=9 Hz, J=2.5 Hz, 1H), 8.80 (d, J=2 Hz, 1H), 9.15 (d, J=2 Hz, 1H), 10.83 (brs, 1H); ESIMS found for C25H25N7O2 m/z 456.4 (M+H).

Workup

  1. additionbefore pouring into ice
  2. customThe solids formed
  3. filtrationwere filtered
  4. washwashed
  5. washwith cold washed
  6. customdried under vacuum
  7. additiona few drops of MeOH were added
  8. filtrationThe insoluble solids were filtered
  9. concentrationThe filtrate was concentrated
  10. filtrationfiltered
  11. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-2092f7f90d2049d0a88789601de75f39
Source dataset
uspto-grants-2014_04
Patent number
US08697887B2

Reaction notes

Loading…