Sodium Bicarbonate → 1,1-dimethylethyl 4-(6-{5-[(ethylamino)carbonyl]-3-fluoro-2-methylphenyl}-1H-indazol-3-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate

HRID 2246626Notes

Reaction equation

HRID 2246626 reaction equation
[CH2:1]([NH:3][C:4](=[O:23])[C:5]1[CH:10]=[C:9]([C:11]2[CH:19]=[C:18]3[C:14]([C:15](I)=[N:16][NH:17]3)=[CH:13][CH:12]=2)[C:8]([CH3:21])=[C:7]([F:22])[CH:6]=1)[CH3:2].CC1(C)C(C)(C)OB([C:32]2[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:36][CH:37]=2)O1.C(=O)([O-])O.[Na+]>C(O)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([NH:3][C:4]([C:5]1[CH:6]=[C:7]([F:22])[C:8]([CH3:21])=[C:9]([C:11]2[CH:19]=[C:18]3[C:14]([C:15]([C:32]4[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH:33]=4)=[N:16][NH:17]3)=[CH:13][CH:12]=2)[CH:10]=1)=[O:23])[CH3:2]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 178464894HCID 178464894, compound2×

Product 1

HCID 588996041,1-dimethylethyl 4-(6-{5-[(ethylamino)carbonyl]-3-fluoro-2-methylphenyl}-1H-indazol-3-yl)-3,6-dihydro-1(2H)-pyridinecarboxylateYield 66.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of N-ethyl-3-fluoro-5-(3-iodo-1H-indazol-6-yl)-4-methylbenzamide (Intermediate 19, 2.34 g), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (1.71 g), aqueous sodium hydrogen carbonate (1M, 11.1 ml) and tetrakis(triphenylphosphine)palladium(0) (129 mg) in isopropanol (10 ml) was divided into three portions then stirred in sealed vials at 150° C. for 25 min in a microwave oven. The reaction mixtures were combined, the solvent was removed under vacuum and the residue was partitioned between ethyl acetate and water. The organic layer was separated using a hydrophobic filter tube, the solvent was evaporated and the residue was purified by chromatography on a silica column eluting with an ethyl acetate:cyclohexane gradient, to give the title compound as a yellow foam (1.76 g).

Workup

  1. customThe reaction mixtures
  2. customthe solvent was removed under vacuum
  3. customthe residue was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. customthe solvent was evaporated
  6. customthe residue was purified by chromatography on a silica column
  7. washeluting with an ethyl acetate

Sources & evidence

ORD record
ord-38c79a5b6eac44198382e48a4a5dfdf0
Source dataset
uspto-grants-2010_03
Patent number
US07687532B2

Reaction notes

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