1,4-Dioxane → HCID 178452069, compound

HRID 1909037Notes

Reaction equation

HRID 1909037 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:20]=[C:19]3[NH:21][C:22]([C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28](Br)[CH:27]=4)=[O:25])=[N:23][C:18]3=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[CH:35][N:34]1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:20]=[C:19]3[NH:21][C:22]([C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28]([C:36]5[C:37]6[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=6)[CH:33]=[N:34][CH:35]=5)[CH:27]=4)=[O:25])=[N:23][C:18]3=[CH:17][CH:16]=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 66599946HCID 66599946, compoundHCID 178452068HCID 178452068, compound

Product 1

HCID 178452069HCID 178452069, compoundYield 34.1%

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]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (40 mg, 0.08 mmole), 2-isoquinoline boronic acid (13.8 mg, 0.08 mmole), Pd(Ph3)4 (27.6 mg, 0.24 mmole), 2 molar of K3PO4 aqueous (0.08 ml, 0.16 mmole), and dioxane (3.0 ml) was degassed and heated to 120° C. for 20 minutes in microwave. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated. Residue was purified by using silica gel chromatography, eluting with 50% to 100% of EtOAc in CH2Cl2 to afford [4-[2-(2-isoquinolin-4-yl-pyridine-4-carbonyl)-3H-imidazo[4.5-b]pyridine-5-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (15 mg, 34%). 1H NMR (400 MHz, CD2Cl2) δ 1.27 (d, 9H), 1.89 (m, 2H), 325 (m, 2H), 3.51 (m, 2H), 3.66 (m, 2H), 3.78 (m, 2H), 6.65 (d, J=9.03 Hz, 1H), 7.61 (t, J=7.53 Hz, J=7.53 Hz, 1H), 7.69 (t, J=7.53 Hz, J=7.53 Hz, 1H), 7.84 (d, J=9.03 Hz, 1H), 8.03 (d, J=8.03 Hz, 1H), 8.27 (d, J=8.03 Hz, 1H), 8.39 (d, J=4.52 Hz, 1H), 8.66 (s, 1H), 8.71 (s, 1H), 8.95 (d, J=5.02 Hz, 1H), 9.28 (s, 1H). HR-MS m/z 550.2570 [M+1].

Workup

  1. customwas degassed
  2. customReaction solution
  3. extractionextracted with EtOAc
  4. concentrationEtOAc layer was concentrated
  5. customResidue was purified
  6. washeluting with 50% to 100% of EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-a6997009765b479ab68d958934b60a05
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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