4-[1-(3-Hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one → 7-amino-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-2,3-dihydro-1H-isoindol-1-one
Reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[C:15]3[C:11]=2[CH2:12][N:13]([CH3:23])[C:14]3=[O:22])[CH:7]=[N:6]1>CCO.[Pd]>[NH2:19][C:16]1[CH:17]=[CH:18][C:10]([C:8]2[CH:7]=[N:6][N:5]([CH2:4][CH2:3][CH2:2][OH:1])[CH:9]=2)=[C:11]2[C:15]=1[C:14](=[O:22])[N:13]([CH3:23])[CH2:12]2Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Procedure
A suspension of 4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one (Compound 1D, 920 mg, 2.91 mmol) and 10% Pd/C (50% H2O) (1.41 g, 0.66 mmol) in EtOH (85 mL) was hydrogenated at rt for 2 h. The crude mixture was filtered through a pad of Celite, rinsed thoroughly with MeOH and EtOAc, concentrated in vacuo, and purified using a Teledyne ISCO CombiFlash® Rf system (eluting with 0-5% MeOH:CH2Cl2) to isolate the desired compound as 634 mg as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J=0.5 Hz, 1H), 7.71 (d, J=0.8 Hz, 1H), 7.43 (d, J=8.3 Hz, 1H), 6.61 (d, J=8.3 Hz, 1H), 6.05 (s, 2H), 4.59 (t, J=5.1 Hz, 1H), 4.45 (s, 2H), 4.17 (t, J=7 Hz, 2H), 3.41 (q, J=6.1 Hz, 2H), 3.03 (s, 3H), 1.94 (quin, J=6.1 Hz, 2H). MS (ESI): m/z 287.13 [M+H]+. UPLC: tR=0.89 min (UPLC-TOF: polar—3 min).
Workup
- filtrationThe crude mixture was filtered through a pad of Celite
- washrinsed thoroughly with MeOH and EtOAc
- concentrationconcentrated in vacuo
- custompurified
- washa Teledyne ISCO CombiFlash® Rf system (eluting with 0-5% MeOH:CH2Cl2)
Sources & evidence
- ORD record
- ord-ffb0f0fce2b24c65b02186c8e9823ba9
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133224B2
Reaction notes
Loading…