Pyridine → HCID 45254393, compound

HRID 872392Notes

Reaction equation

HRID 872392 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-ce087c4f3762494996ad2369965db36e
Source dataset
uspto-grants-2015_03
Patent number
US08975285B2

Reaction notes

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