Toluene → N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamide

HRID 602417Notes

Reaction equation

HRID 602417 reaction equation
[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH2:11])[CH:7]=[CH:8]2)=[N:3]1.C[Al](C)C.C1(C)C=CC=CC=1.C[O:24][C:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][C:27]=1[NH:32][CH2:33][C:34]1[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41]([NH:43][CH3:44])=[O:42])[CH:35]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>ClCCCl>[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH:11][C:25](=[O:24])[C:26]3[CH:31]=[CH:30][CH:29]=[N:28][C:27]=3[NH:32][CH2:33][C:34]3[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41]([NH:43][CH3:44])=[O:42])[CH:35]=3)[CH:7]=[CH:8]2)=[N:3]1

Participants

7

Reactant 5

HCID 1140TolueneHCID 5902202-Methyl-2H-indazol-6-amineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 586749452-{[2-(3-Methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinic acid methyl ester

Product 1

HCID 11611709N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamideYield 53%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
85 °C

Procedure

A suspension of 2-methyl-2H-indazol-6-ylamine [Davies J. Chem. Soc.; 1955; 2412-2419] (809 mg, 5.5 mmol) in DCE (13.5 mL) was treated at 0° C. consecutively with, trimethylaluminium (2 M) in toluene (4.23 mL, 8.46 mmol), 2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinic acid methyl ester (1.34 g, 4.23 mmol) and DCE (20 mL). The reaction mixture was placed under a nitrogen atmosphere and heated for 10 hours at 85° C. (bath temperature). On cooling the reaction was poured into aqueous sodium-potassium tartrate solution (150 mL) and partitioned between EtOAc and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (Gradient elution: 100% CH2Cl2 to 90% CH2Cl2/10% MeOH) to give N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamide (964 mg, 53%) as a solid; Mp. 205-207° C.

Workup

  1. temperatureOn cooling the reaction
  2. custompartitioned between EtOAc and water
  3. washThe organic phase was washed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on silica gel (Gradient elution: 100% CH2Cl2 to 90% CH2Cl2/10% MeOH)

Sources & evidence

ORD record
ord-d2ef29d827fd4511b2b807b41a627d4d
Source dataset
uspto-grants-2011_03
Patent number
US07906533B2

Reaction notes

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