Water → 4-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-c]pyridin-3-amine

HRID 1910074Notes

Reaction equation

HRID 1910074 reaction equation
Cl[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([C:19](=O)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=2)[CH2:14][CH2:13]3)[C:7]=1[C:8]#[N:9].[OH2:29].[NH2:30][NH2:31].O>C(O)C>[CH3:27][C:23]1[CH:22]=[C:21]([CH2:20][C:19]([N:15]2[C:16]3[C:12](=[CH:11][C:10]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]5[NH:30][N:31]=[C:8]([NH2:9])[C:7]=45)=[CH:18][CH:17]=3)[CH2:13][CH2:14]2)=[O:29])[CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 668238123-chloro-5-{1-[(3-methyl phenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-4-pyridinecarbonitrile

Product 1

HCID 668237694-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-c]pyridin-3-amineYield 15.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To 3-chloro-5-{1-[(3-methyl phenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-4-pyridinecarbonitrile (100 mg, 0.258 mmol) in Ethanol (6 mL) was added hydrazine monohydrate (1 mL, 31.9 mmol), and the reaction mixture was stirred at 80° C. overnight into a sealed vessel. LCMS analysis of the reaction mixture indicated the presence of starting material. Therefore, the reaction mixture was stirred at 100° C. overnight. The mixture was poured onto EtOAc and water. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The resulting residue was purified by flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc to 20% CH3OH/EtOAc). The fractions containing the product were combined, concentrated, and triturated with Et2O to afford 4-{1-[(3-methyl phenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-c]pyridin-3-amine (15 mg) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 2.32 (s, 3H), 3.25 (t, J=8.34 Hz, 2H), 3.85 (s, 2H), 4.24 (t, J=8.46 Hz, 2H), 4.6 (m, 1.3H(NH2)), 7.05-7.16 (m, 3H), 7.19-7.28 (m, 1H), 7.33 (d, J=8.34 Hz, 1H), 7.42 (s, 1H), 7.93 (s, 1H), 8.21 (d, J=8.34 Hz, 1H), 8.74 (s, 1H), 12.27 (br. s., 1H).

Workup

  1. stirringTherefore, the reaction mixture was stirred at 100° C. overnight
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc to 20% CH3OH/EtOAc)
  8. additionThe fractions containing the product
  9. concentrationconcentrated
  10. customtriturated with Et2O

Sources & evidence

ORD record
ord-3fe43fc1a110485481318376dc5a9184
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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