1,4-Dioxane → HCID 178434141, compound

HRID 1909044Notes

Reaction equation

HRID 1909044 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[C:18]3[NH:20][C:21]([C:23]([C:25]4[CH:30]=[CH:29][N:28]=[C:27](Br)[CH:26]=4)=[O:24])=[N:22][C:17]3=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:32]([O:36][C:37]([N:39]1[C:43]([CH3:44])=[C:42](B2OC(C)(C)C(C)(C)O2)[C:41]([CH3:54])=[N:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[C:18]3[NH:20][C:21]([C:23]([C:25]4[CH:30]=[CH:29][N:28]=[C:27]([C:42]5[C:41]([CH3:54])=[N:40][N:39]([C:37]([O:36][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:38])[C:43]=5[CH3:44])[CH:26]=4)=[O:24])=[N:22][C:17]3=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 162183871-(tert-Butoxycarbonyl)-3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazoleHCID 178452223HCID 178452223, compound

Product 1

HCID 178434141HCID 178434141, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

The mixture of [4-[2-(2-bromo-pyridine-4-carbonyl)-3H-imidazo[4,5-b]pyridine-5-yl]-piperazine-1-carboxylic acid tert-butyl ester (Example 164) (100 mg, 0.205 mmole), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (Example 167) (66 mg, 0.205 mmole), Pd(Ph3)4 (23 mg, 0.021 mmole), 2 molar of K3PO4 aqueous (0.21 ml, 0.41 mmole), and dioxane (3.0 ml) was degassed and heated to 120° C. for 40 minutes in microwave. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated to afford 120 mg of crude 4-{2-[2-(1-tert-butoxycarbonyl-3,5-dimethyl-1H-pyrazol-4-yl)-pyridine-4-carbonyl]-3H-imidazo[4,5-b]pyridin-5-yl}-piperazine-1-carboxylic acid tert-butyl ester, which was dissolved in 3 ml of 2 molar HCl ether solution. The acidic solution was stirred for 2 hours, then solvent was removed. Residue was washed with EtOAc and was purified by using HPLC, eluting with 10 to 20% of acetonitrile in water (0.1% of NH4OH) to yield [2-(3,5-Dimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-(5-piperazin-1-yl-3H-imidazo[4,5-b]pyridine-2-yl)-methanon (20 mg, 24%) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 2.41 (s, 6H), 2.94 (m, 4H), 3.61 (m, 4H), 6.88 (d, J=9.03 Hz, 1H), 7.87 (d, J=9.03 Hz, 1H), 7.94 (d, J=5.02 Hz, 1H), 8.17 (s, 1H), 8.76 (d, J=5.02 Hz, 1H). HR-MS m/z 403.1981 (M+1).

Workup

  1. customwas degassed
  2. customReaction solution
  3. extractionextracted with EtOAc
  4. concentrationEtOAc layer was concentrated

Sources & evidence

ORD record
ord-d7970db7051b44268dde38848e79cc7e
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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