1,1'-Carbonyldiimidazole → HCID 58416754, compound

HRID 1916818Notes

Reaction equation

HRID 1916818 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C1N=CN([C:23](N2C=NC=C2)=[O:24])C=1.[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][C:43]2[CH:48]=[CH:47][N:46]=[C:45]([NH2:49])[N:44]=2)=[CH:33][CH:32]=1>C(Cl)Cl>[NH2:49][C:45]1[N:44]=[C: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:23]([NH:10][C:8]3[N:7]([C:11]4[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=4)[N:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:9]=3)=[O:24])=[CH:32][CH:33]=2)[CH:48]=[CH:47][N:46]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 584167554-((4-Aminonaphthalen-1-yloxy)methyl)pyrimidin-2-amine

Product 1

HCID 58416754HCID 58416754, compoundYield 38.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (4) (WO 2000043384) (0.98 g, 4.26 mmol) in DCM (4.0 mL) was added dropwise over 1 hr, to a suspension of CDI (0.69 g, 4.26 mmol) in DCM (3.0 mL) and the solution was stirred at RT for 2 hr. This solution was added dropwise to a solution of 4-((4-aminonaphthalen-1-yloxy)methyl)pyrimidin-2-amine (33) (0.9 g, 2.366 mmol) in DCM (10 mL). After each 1.0 mL aliquot was added, the reaction was allowed to stir for 1 hr, and the mixture monitored by LC-MS to ensure consumption of the CDI activated 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine, without over acylation. The reaction was quenched with MeOH (20 mL), silica added (20 g) and the volatiles evaporated. The residue was subjected to column chromatography (100 g) eluting with 50 to 100% EtOAc in iso-hexane. The combined fractions were triturated from DCM (20 mL) and the solid collected, and washed with diethyl ether (50 mL) to give 1-(4-((2-aminopyrimidin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate H) as a purple solid (0.48 g, 38%): m/z 523 (M+H)+ (ES+).

Workup

  1. additionAfter each 1.0 mL aliquot was added
  2. stirringto stir for 1 hr
  3. customconsumption of the CDI
  4. customThe reaction was quenched with MeOH (20 mL), silica
  5. additionadded (20 g)
  6. customthe volatiles evaporated
  7. washeluting with 50 to 100% EtOAc in iso-hexane
  8. customThe combined fractions were triturated from DCM (20 mL)
  9. customthe solid collected
  10. washwashed with diethyl ether (50 mL)

Sources & evidence

ORD record
ord-e9658a1ccc9148249dabf8462ccd9bf3
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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