Sodium Carbonate → HCID 71526618, compound

HRID 1755416Notes

Reaction equation

HRID 1755416 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:24]([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[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]>[C:24]([C:28]1[CH:33]=[CH:32][C:31]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[CH2:22][CH2:21][CH2:20][CH:19]4[CH3:23])[N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)=[CH:30][CH:29]=1)([CH3:27])([CH3:26])[CH3:25]

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 71526618HCID 71526618, compoundYield 38.4%

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 (60 mg, 0.183 mmol) and 4-tert-butylphenylboronic acid (49 mg, 0.274 mmol) in dioxane/H2O (10 mL/1 mL) was added Na2CO3 (39 mg, 0.366 mmol) followed by Pd(dba)2 (21 mg) and X-Phos (9 mg) under nitrogen with stirring. The mixture was refluxed for 15 h under nitrogen. After cooling, the solvent was concentrated in vacuo. The residue was purified by chromatography (silica, dichloromethane:MeOH=100:1) to give 6-(4-tert-butylphenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyri-dazin-8-amine (30 mg, 38%) as a solid. 1H NMR (300 MHz, CDCl3): δ 8.70 (s, 1H), 8.30 (brs, 1H), 7.90 (d, 1H, J=7.5 Hz), 7.60 (s, 1H), 7.51-7.38 (m, 4 h), 6.31 (d, 1H, J=7.2 Hz), 6.03 (d, 1H, J=8.1 Hz), 4.24 (brs, 1H), 3.66 (brs, 1H), 3.49-3.47 (m, 1H), 2.15-2.09 (m, 3H), 1.75 (brs, 1H), 1.38 (s, 9H), 1.23 (d, 3H, J=6.3 Hz). LC/MS: 427 [M+H]+, tR=2.51 min. HPLC: 95.63% at 214 nm, 99.19% at 254 nm, tR=99.79% min.

Workup

  1. temperatureThe mixture was refluxed for 15 h under nitrogen
  2. temperatureAfter cooling
  3. concentrationthe solvent was concentrated in vacuo
  4. customThe residue was purified by chromatography (silica, dichloromethane:MeOH=100:1)

Sources & evidence

ORD record
ord-d7b1a5a0b5194ad39fd21e1e7c49b0d7
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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