1,1'-Carbonyldiimidazole → tert-butyl-4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido) naphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate

HRID 1916797Notes

Reaction equation

HRID 1916797 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[C:13]([C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14].[NH2:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([O:41][CH2:42][CH2:43][C:44]2[CH:49]=[CH:48][N:47]=[C:46]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH:45]=2)=[CH:33][CH:32]=1>C(Cl)Cl.CO>[C:53]([O:52][C:51](=[O:57])[NH:50][C:46]1[CH:45]=[C:44]([CH2:43][CH2:42][O:41][C:34]2[C:35]3[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:31]([NH:30][C:6]([NH:22][C:20]3[N:19]([C:23]4[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=4)[N:18]=[C:17]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:21]=3)=[O:7])=[CH:32][CH:33]=2)[CH:49]=[CH:48][N:47]=1)([CH3:54])([CH3:56])[CH3:55]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 58416770tert-Butyl 4-(2-(4-aminonaphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate

Product 1

HCID 58416761tert-butyl-4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido) naphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamateYield 83.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a suspension of CDI (3.00 g, 18.18 mmol) in DCM (15 mL) was added a solution of 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (4) (WO 2000043384) (4.17 g, 18.18 mmol) in DCM (40 mL) over 1.5 hrs. After stirring at RT for 2 hr, a solution of tert-butyl 4-(2-(4-aminonaphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate (13) (3.00 g, 7.91 mmol) in DCM (15 mL) was added. After stirring overnight, the solution was diluted with MeOH (10 mL) and absorbed onto silica gel (30 g) and subjected to column chromatography (330 g) eluting with 30% to 100% EtOAc in iso-hexane and then 0% to 6% MeOH in EtOAc to give tert-butyl-4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate (13) as a beige solid (4.20 g, 80%): m/z 635 (M+H)+ (ES+).

Workup

  1. stirringAfter stirring overnight
  2. customabsorbed onto silica gel (30 g)
  3. washeluting with 30% to 100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-5ae917a39f01454b81812daf9e6c5e59
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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