Pyridine → HCID 45254393, compound

HRID 2067053Notes

Reaction equation

HRID 2067053 reaction equation
[CH3:1][N:2]=[C:3]=[O:4].N[C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[CH2:12][O:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([NH:24][C:25]([NH:27][C:28]2[N:32]([C:33]3[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=3)[N:31]=[C:30]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:29]=2)=[O:26])=[CH:16][CH:15]=1.[N:44]1C=CC=CC=1>>[CH3:1][NH:2][C:3](=[O:4])[NH:44][C:9]1[CH:10]=[C:11]([CH2:12][O:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([NH:24][C:25]([NH:27][C:28]3[N:32]([C:33]4[CH:34]=[CH:35][C:36]([CH3:39])=[CH:37][CH:38]=4)[N:31]=[C:30]([C:40]([CH3:42])([CH3:43])[CH3:41])[CH:29]=3)=[O:26])=[CH:16][CH:15]=2)[CH:6]=[CH:7][N:8]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 12228Methyl Isocyanate2×HCID 58416751HCID 58416751, compound2×

Product 1

HCID 45254393HCID 45254393, compoundYield 14%

Procedure

Methyl isocyanate (8.5 μl, 0.14 mmol) was added to a solution of 1-(4-((3-aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate C) (50 mg, 0.10 mmol) in pyridine (1.0 mL). The reaction mixture was stirred for 2 hr at RT and a further portion of methyl isocyanate (8.5 μl, 0.14 mmol) was added and stirring continued for 72 hr at RT. The solvent was removed in vacuo and the crude product was purified by column chromatography (4 g, 10-25% MeOH in DCM, gradient elution). The crude product fractions were combined and triturated with DCM (20 mL). The solid was filtered off to afford 1-(4-((3-methylureidopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Example 15) (8 mg, 14%): m/z 578 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 2.39 (3H, s), 2.68 (3H, d), 5.27 (2H, s), 6.35 (1H, s), 6.53 (1H, m), 6.98 (1H, d), 7.35 (2H, d), 7.45 (2H, d), 7.65-7.52 (4H, m), 7.92 (1H, d), 8.16 (1H, s), 8.28 (2H, m), 8.61 (1H, s), 8.82 (1H, s), 8.88 (1H, s).

Workup

  1. stirringstirring
  2. waitcontinued for 72 hr at RT
  3. customThe solvent was removed in vacuo
  4. customthe crude product was purified by column chromatography (4 g, 10-25% MeOH in DCM, gradient elution)
  5. customtriturated with DCM (20 mL)
  6. filtrationThe solid was filtered off

Sources & evidence

ORD record
ord-92b95558054545128026ace360fbd4d5
Source dataset
uspto-grants-2012_10
Patent number
US08293748B2

Reaction notes

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