Diethyl Ether → HCID 54739184, compound

HRID 1822426Notes

Reaction equation

HRID 1822426 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][N:9]1[C:14](=[O:15])[C:13]([C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17])=[C:12]([OH:23])[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10]1.CC1(C)C(C)(C)OB([C:35]2[CH:40]=[CH:39][N:38]=[C:37]([N:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)[CH:36]=2)O1.C(=O)([O-])[O-].[K+].[K+].CCOCC>O1CCOCC1.O.Cl.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>[OH:23][C:12]1[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10][N:9]([CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[C:35]2[CH:40]=[CH:39][N:38]=[C:37]([N:41]3[CH2:42][CH2:43][NH:44][CH2:45][CH2:46]3)[CH:36]=2)[C:14](=[O:15])[C:13]=1[C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17]

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 162179482-(1-Piperaziny) pyridine-4-boronic acid pinacol esterHCID 54739212N-{[2-[(2-Bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

Product 1

HCID 54739184HCID 54739184, compoundYield 47%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a 5 mL microwave tube was added N-{[2-[(2-bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 78(b), 75 mg, 0.177 mmol), 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (51.1 mg, 0.177 mmol), potassium carbonate (73.3 mg, 0.530 mmol), and tetrakis(triphenylphosphine)palladium (0) (6.13 mg, 5.30 μmol) in 1,4-Dioxane (1.5 ml) and Water (0.500 ml). The mixture was irradiated at 100° C. for 20 minutes. The reaction mixture was diluted with water (3 ml) and 1N HCl (1 mL). The mixture was then filtered to remove residual salts and purified by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA)). The title compound, N-{[5-hydroxy-6-(1-methylethyl)-3-oxo-2-({2-[2-(1-piperazinyl)-4-pyridinyl]phenyl}methyl)-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (52 mg, 0.083 mmol, 47.0% yield), was obtained as a white solid (tfa salt) after trituration with ether. 1H NMR (400 MHz, DMSO-d6) d ppm 15.83 (s, 1 H), 13.02 (br. s., 1H), 10.07 (t, J=5.43 Hz, 1H), 8.79 (br. s., 2H), 8.19 (d, J=5.05 Hz, 1H), 7.39 (dd, J=5.68, 3.41 Hz, 2H), 7.24-7.31 (m, 1H), 7.21 (dd, J=5.43, 3.66 Hz, 1H), 6.93 (s, 1H), 6.78 (d, J=5.05 Hz, 1H), 5.30 (s, 2H), 4.08 (d, J=5.56 Hz, 2H), 3.69-3.85 (m, 4H), 3.20 (br. s., 4H), 3.12 (m, 1H), 1.12 (d, J=6.82 Hz, 6H). MS (ES+) m/e 507 [M+H]+.

Workup

  1. customThe mixture was irradiated at 100° C. for 20 minutes
  2. filtrationThe mixture was then filtered
  3. customto remove residual salts
  4. custompurified by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA))

Sources & evidence

ORD record
ord-a3e858a592da420c9be72182ba2dc27d
Source dataset
uspto-grants-2009_10
Patent number
US07608621B2

Reaction notes

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