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2-Methyl-2H-indazol-6-amine → 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamide

HRID 602426
Notes
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Reaction equation

HRID 602426 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.C[O:17][C:18](=O)[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][C:20]=1[NH:25][CH2:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([Cl:33])[CH:28]=1>ClCCCl>[Cl:33][C:29]1[CH:28]=[C:27]([CH2:26][NH:25][C:20]2[N:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18]([NH:11][C:6]2[CH:7]=[CH:8][C:9]3[C:4]([CH:5]=2)=[N:3][N:2]([CH3:1])[CH:10]=3)=[O:17])[CH:32]=[CH:31][N:30]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 5902202-Methyl-2H-indazol-6-amineHCID 16682925TrimethylaluminumHCID 586749472-[(2-Chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl ester

Product 1

HCID 586749502-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamideYield 77.2%

Reagents, catalysts & solvents 1

HCID 11
1,2-Dichloroethane
Solvent
2×

Conditions

Temperature
100 °C

Procedure

To a stirred and chilled (0° C.) suspension of 2-methyl-2H-indazol-6-ylamine (1.52 g) in DCE (6 mL), under nitrogen, was added trimethylaluminium (2M solution in toluene, 5 mL, 9.37 mmol). This mixture was added dropwise to a stirred and chilled (0° C.) solution of 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl ester (1.45 g, 5.21 mmol) in DCE (14.7 mL). The mixture was heated at 100° C. for 2 hours before cooling to room temperature and quenching by pouring into aqueous sodium-potassium tartrate solution. The mixture was extracted with EtOAc and the combined organic layers washed successively with dilute aqueous citric acid solution, dilute aqueous sodium hydrogen carbonate solution and brine, dried and concentrated in vacuo to give 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamide (1.58 g); 1H-NMR (300 MHz, d6-DMSO) 10.26 (1H, s), 8.40 (1H, t), 8.28 (1H, d), 8.25 (1H, s), 8.06-8.12 (3H, m), 7.62 (1H, d), 7.35 (1H, s), 7.30 (1H, unresolved dd), 7.27 (1H, unresolved dd), 6.68 (1H, dd), 4.67 (2H, d), 4.10 (3H, s).

Workup

  1. temperaturechilled
  2. additionThis mixture was added dropwise to
  3. stirringa stirred
  4. temperaturebefore cooling to room temperature
  5. customquenching
  6. additionby pouring into aqueous sodium-potassium tartrate solution
  7. extractionThe mixture was extracted with EtOAc
  8. washthe combined organic layers washed successively with dilute aqueous citric acid solution, dilute aqueous sodium hydrogen carbonate solution and brine
  9. customdried
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ab16cb210a6e4970b5ee0826868b25da
Source dataset
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07906533B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes