N'-[4-(1-ethyl-4-{2-[3-(hydroxymethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-N,N-dimethylurea → N'-(4-{1-ethyl-4-[2-(3-formylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-pyrazol-3-yl}phenyl)-N,N-dimethylurea

HRID 28912Notes

Reaction equation

HRID 28912 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][OH:24])[CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:36])[N:33]([CH3:35])[CH3:34])=[CH:27][CH:26]=2)=[N:4]1)[CH3:2]>C(Cl)(Cl)Cl.O=[Mn]=O>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]=[O:24])[CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:25]2[CH:26]=[CH:27][C:28]([NH:31][C:32](=[O:36])[N:33]([CH3:35])[CH3:34])=[CH:29][CH:30]=2)=[N:4]1)[CH3:2]

Participants

4

Reactant 1

HCID 58980000N'-[4-(1-ethyl-4-{2-[3-(hydroxymethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-N,N-dimethylurea

Product 1

HCID 58980006N'-(4-{1-ethyl-4-[2-(3-formylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-pyrazol-3-yl}phenyl)-N,N-dimethylureaYield 81.1%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of N′-[4-(1-ethyl-4-{2-[3-(hydroxymethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-N,N-dimethylurea (16.67 g, 85% pure, 29.5 mMol) in CHCl3 (700 mL) was added activated MnO2 (33 g, 380 mMol). The reaction was stirred and refluxed (70° C. oil bath) for 6 h, cooled to RT, filtered through a pad of Celite®, rinsed with CHCl3, and evaporated to dryness under vacuum. Purification by flash chromatography on silica gel (5 to 15% MeOH in (1:1) EtOAc/CHCl3) gave the title product (11.45 g, 81%) as a yellow solid (>95% pure by HPLC): MS (ES) m/e 479.3 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 12.33 (d, J=1.3 Hz, 1H), 10.07 (s, 1H), 8.44 (s, 1H), 8.31 (s, 1H), 8.29 (s, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.11 (d, J=5.1 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.69 (t, J=7.7 Hz, 1H), 7.43 (d, J=8.6 Hz, 2H), 7.28 (d, J=8.6 Hz, 2H), 6.95 (d, J=2.0 Hz, 1H), 6.81 (d, J=5.1 Hz, 1H), 4.28 (q, J=7.2 Hz, 2H), 2.91 (s, 6H), 1.52 (t, J=7.3 Hz, 3H).

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered through a pad of Celite®
  3. washrinsed with CHCl3
  4. customevaporated to dryness under vacuum
  5. customPurification by flash chromatography on silica gel (5 to 15% MeOH in (1:1) EtOAc/CHCl3)

Sources & evidence

ORD record
ord-a40ec246f57f44b7bddda723388d7c6a
Source dataset
uspto-grants-2008_09
Patent number
US07419988B2

Reaction notes

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