Potassium Carbonate → HCID 71451823, compound

HRID 1755390Notes

Reaction equation

HRID 1755390 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18]3[CH2:22][CH2:21][CH2:20][CH:19]3[CH3:23])[N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[OH:24][CH2:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:23][CH:19]1[CH2:20][CH2:21][CH2:22][N:18]1[C:14]1[N:13]=[C:12]([NH:11][C:4]2[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=[C:2]([C:30]3[CH:31]=[C:26]([CH2:25][OH:24])[CH:27]=[CH:28][CH:29]=3)[CH:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 715343846-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 71451823HCID 71451823, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (500 mg, 1.52 mmol), 3-(hydroxymethyl)phenylboronic acid (350 mg, 2.28 mmol), Pd2dba3 (100 mg, 0.15 mmol), X-phos (300 mg, 0.61 mmol) and K2CO3 (625 mg, 4.56 mmol) was dissolved in dioxane/water (50 mL/5 mL). The reaction mixture was degassed with bubbling nitrogen for 5 minutes then heated at 100° C. with stirring for 3 h, the solvent removed in vacuo, The residue purified by chromatography (silica gel, 200-300 mesh, dichloromethane/methanol=40:1) to give (3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenyl)methanol (300 mg, 81%) as a white solid. 1H NMR (300 MHz, DMSO): δ 9.62 (s, 1H), 8.77 (s, 1H), 8.19 (s, 1H), 7.88 (s, 1H), 7.81-7.78 (m, 1H), 7.63 (s, 1H), 7.49-7.39 (m, 3H), 6.71 (d, 1H, J=7.8 Hz), 6.05 (d, 1H, J=7.8 Hz), 5.31 (t, 1H, J=5.7 Hz), 4.59 (d, 2H, J=5.7 Hz), 4.25-4.20 (m, 1H), 3.58-3.50 (m, 1H), 3.42-3.38 (m, 1H), 2.08-1.97 (m, 3H), 1.70 (brs, 1H), 1.11 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 401, tR=1.679 min, HPLC: 99.87% at 214 nm, 99.85% at 254 nm, tR=5.87 min.

Workup

  1. customThe reaction mixture was degassed with bubbling nitrogen for 5 minutes
  2. customthe solvent removed in vacuo
  3. customThe residue purified by chromatography (silica gel, 200-300 mesh, dichloromethane/methanol=40:1)

Sources & evidence

ORD record
ord-8590d02d62f141e0be7ca8cb6a15d2de
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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