Sodium Bicarbonate → HCID 11712238, compound

HRID 600677Notes

Reaction equation

HRID 600677 reaction equation
[CH3:1][N:2]1[C:10]([CH3:11])=[C:9]2[C:4]([CH:5]=[C:6]([NH2:12])[CH:7]=[CH:8]2)=[N:3]1.C[Al](C)C.C[O:18][C:19](=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[NH:26][CH2:27][C:28]1[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]([N:37]([CH3:39])[CH3:38])=[O:36])[CH:29]=1.C(=O)([O-])O.[Na+]>ClCCCl.ClCCl>[CH3:1][N:2]1[C:10]([CH3:11])=[C:9]2[C:4]([CH:5]=[C:6]([NH:12][C:19](=[O:18])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[NH:26][CH2:27][C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]([N:37]([CH3:38])[CH3:39])=[O:36])[CH:29]=3)[CH:7]=[CH:8]2)=[N:3]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 115428272,3-Dimethyl-2H-indazol-6-amineHCID 16682925TrimethylaluminumHCID 67051939HCID 67051939, compound

Product 1

HCID 11712238HCID 11712238, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2,3-dimethyl-2H-indazol-6-ylamine (60 mg, 0.34 mmol) in DCE (1.5 mL) at 0° C., under nitrogen, was added trimethylaluminium (2M in toluene, 0.35 mL, 0.7 mmol), followed by a solution of 2-{[2-(3,3-dimethyl-ureido)-pyridin-4-ylmethyl]-amino}-benzoic acid methyl ester (111 mg, 0.34 mmol) in DCE (1.5 mL). The reaction was heated at 100° C. (bath temperature) for 5 hours. On cooling the reaction was poured onto saturated aqueous sodium hydrogencarbonate solution and diluted with dichloromethane. The mixture was stirred for 15 minutes before filtering through Celite®. The organic phase was washed with water and brine, dried, and concentrated in vacuo. The residue was purified by repeated chromatography on Isolute® flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 95:5) to give N-(2,3-dimethyl-2H-indazol-6-yl)-2-{[2-(3,3-dimethyl-ureido)-pyridin-4-ylmethyl]-amino}-benzamide (23 mg, 15%) as a solid; 1H-NMR (300 MHz, d6-DMSO) 10.10 (1H, s), 8.79 (1H, s), 8.15 (1H, d), 8.00 (1H, s), 7.95 (1H, t), 7.82 (1H, s), 7.70-7.73 (1H, m), 7.60 (1H, d), 7.22-7.29 (2H, m), 6.93-6.95 (1H, m), 6.67 (1H, t), 6.53 (1H, d), 4.45 (2H, d), 4.01 (3H, s), 2.91 (6H, s), 2.59 (3H, s); m/z (ES+) 458 [M+H]+, 230.

Workup

  1. temperatureOn cooling the reaction
  2. filtrationbefore filtering through Celite®
  3. washThe organic phase was washed with water and brine
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified

Sources & evidence

ORD record
ord-b8b15093cf3e45e292f3ab3407da52e8
Source dataset
uspto-grants-2011_03
Patent number
US07902229B2

Reaction notes

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