Hydrazine → Uprosertib

HRID 1845643Notes

Reaction equation

HRID 1845643 reaction equation
[Cl:1][C:2]1[O:6][C:5]([C:7]([NH:9][C@H:10]([CH2:20][N:21]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=2)=[O:8])=[CH:4][C:3]=1[C:32]1[N:36]([CH3:37])[N:35]=[CH:34][C:33]=1[Cl:38].NN>CO>[NH2:21][CH2:20][C@@H:10]([NH:9][C:7]([C:5]1[O:6][C:2]([Cl:1])=[C:3]([C:32]2[N:36]([CH3:37])[N:35]=[CH:34][C:33]=2[Cl:38])[CH:4]=1)=[O:8])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 578266625-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(3,4-difluorophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-2-furancarboxamide

Product 1

HCID 51042438Uprosertib

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(3,4-difluorophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-2-furancarboxamide (304 mg, 0.54 mmol) in methanol (5 ml) at 25° C. was added hydrazine (0.08 ml, 2.7 mmol) dropwise. After 12 h, the solution was concentrated, dry loaded onto silica and purified by column chromatography (5% MeOH in DCM (1% NH4OH)). The free base was converted to the HCl salt by addition of excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml) affording the HCl salt of the title compound as a yellow solid: LC-MS (ES) m/z 430(M+H)+, 1H NMR (400 MHz, MeOD) δ ppm 2.91-3.05 (m, 2H) 3.17-3.28 (m, 2H) 3.81 (s, 3H) 4.57 (d, J=9.60 Hz, 1H) 7.12 (br. s., 1H) 7.18-7.28 (m., 2H) 7.36-7.39 (m, 1H) 7.58 (s, 1H).

Workup

  1. concentrationthe solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (5% MeOH in DCM (1% NH4OH))
  4. additionThe free base was converted to the HCl salt by addition of excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml)

Sources & evidence

ORD record
ord-c09491520650484c82e3ac28d7266af1
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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