Sodium Carbonate → HCID 71526619, compound

HRID 1755417Notes

Reaction equation

HRID 1755417 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.C([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)(C)(C)C.C([O-])([O-])=[O:38].[Na+].[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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.[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:29]3[CH:30]=[C:31]([OH:38])[CH:32]=[CH:33][CH:28]=3)[CH:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27343204-tert-Butylphenylboronic 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 71526619HCID 71526619, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a solution of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (550 mg, 1.68 mmol) and 4-tert-butylphenylboronic acid (345 mg, 2.52 mmol) in dioxane/H2O (20 mL/2 mL) was added Na2CO3 (356 mg, 3.36 mmol) followed by Pd(dba)2 (193 mg, 0.336 mmol) and X-Phos (80 mg, 0.168 mmol) under nitrogen with stirring. The mixture was refluxed for 16 h under nitrogen. After cooling, the solvent was concentrated in vacuo. The residue was purified by chromatography (silica, petroleum ether:EtOAc=3:1 to 1:1) to give 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenol (565 mg, 87%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.61 (s, 1H), 9.58 (s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.62 (s, 1H), 7.44-7.26 (m, 2H), 6.90-6.86 (m, 2H), 6.71 (d, 1H, J=7.8 Hz), 6.05 (d, 1H, J=8.1 Hz), 4.22-4.18 (m, 1H), 3.55-3.53 (m, 1H), 3.42-3.37 (m, 1H), 2.10-1.96 (m, 3H), 1.66 (brs, 1H), 1.13 (d, 3H, J=6.0 Hz). LC/MS: 387 [M+H]+; 385 [M−H]−, tR=1.72 min. HPLC: 95.63% at 214 nm, 95.18% at 254 nm, tR=2.72 min.

Workup

  1. temperatureThe mixture was refluxed for 16 h under nitrogen
  2. temperatureAfter cooling
  3. concentrationthe solvent was concentrated in vacuo
  4. customThe residue was purified by chromatography (silica, petroleum ether:EtOAc=3:1 to 1:1)

Sources & evidence

ORD record
ord-32e2bb97ad174071b12473ddd7b1b848
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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