1,3-Propanediol → HCID 131728754, compound

HRID 604251Notes

Reaction equation

HRID 604251 reaction equation
I[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:16][CH:15]3[N:17]([CH3:18])[CH:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)[CH2:9]2)=[CH:4][CH:3]=1.[S:19]1[CH:23]=[CH:22][C:21](B(O)[OH:25])=[CH:20]1.[C:27](=[O:30])([O-:29])[O-].[K+].[K+].[CH2:33](O)[CH2:34][CH2:35][OH:36].[OH-].[Na+]>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.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O.COCCOC>[C:35]([OH:36])(=[O:25])/[CH:34]=[CH:33]/[C:27]([OH:29])=[O:30].[CH3:18][N:17]1[CH:10]2[CH2:9][N:8]([C:5]3[N:6]=[N:7][C:2]([C:21]4[CH:22]=[CH:23][S:19][CH:20]=4)=[CH:3][CH:4]=3)[CH2:16][CH:15]1[CH2:14][CH2:13][CH2:12][CH2:11]2

Participants

10

Reactant 5

HCID 104421,3-PropanediolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 581760Thiophene-3-boronic acidHCID 86629361HCID 86629361, compound

Product 1

HCID 131728754HCID 131728754, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 8-(6-iodo-pyridazin-3-yl)-10-methyl-8,10-diaza -bicyclo[4.3.1]-decane (1.5 g, 4.19 mmol), 3-thiopheneboronic acid (1.62 g, 12.56 mmol), potassium carbonate (1.74 g, 12.56 mmol), palladacycle (78 mg, 0.084 mmol), Pd(PPh3)4 (97 mg, 0.084 mmol), bis(tri-t-butylphosphine)palladium(0) (43 mg, 0.084 mmol), 1,3-propandiol (0.93 g, 12.6 mmol), DME (60 ml) and water (30 ml) was stirred at reflux for 40 h. Aqueous sodium hydroxide (40 ml, 1 M) was added followed by evaporation of the dioxane and extraction with chloroform (3×40 ml). Chromatography on silica gel with dichloromethane, 10% methanol and 1% aqueous ammonia as solvent gave the title compound as an oil. Yield 0.68 g, 52%. The corresponding salt was obtained by addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. LC-ESI -HRMS of [M+H]+ shows 315.1642 Da. Calc. 315.164342 Da, dev. −0.5 ppm

Workup

  1. temperatureat reflux for 40 h
  2. customfollowed by evaporation of the dioxane and extraction with chloroform (3×40 ml)

Sources & evidence

ORD record
ord-e56faa3a90f5412588dab3f9e33d9ccf
Source dataset
uspto-grants-2011_03
Patent number
US07910578B2

Reaction notes

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