Sodium Carbonate → HCID 71526355, compound

HRID 1755387Notes

Reaction equation

HRID 1755387 reaction equation
[C:1]([CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[C:18]4[N:19]([CH:24]=[CH:25][N:26]=4)[N:20]=[C:21](Cl)[CH:22]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[C:37]([CH:42]=[CH:43][CH:44]=2)[C:38]([O:40][CH3:41])=[O:39])O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Na+].[Na+]>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]>[C:1]([CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[C:18]4[N:19]([CH:24]=[CH:25][N:26]=4)[N:20]=[C:21]([C:35]4[CH:36]=[C:37]([CH:42]=[CH:43][CH:44]=4)[C:38]([O:40][CH3:41])=[O:39])[CH:22]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27346513-Methoxycarbonylphenylboronic acid pinacol esterHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86682737HCID 86682737, compound

Product 1

HCID 71526355HCID 71526355, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-(6-(3-tert-butylpyrrolidin-1-yl)pyridin-2-yl)-6-chloroimidazo[1,2-b]pyridazin-8-amine (400 mg, 1.08 mmol), methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (425 mg, 1.62 mmol), Pd2(dba)3 (64 mg, 0.11 mmol), X-phos (105 mg, 0.22 mmol) and Na2CO3 (343 mg, 3.24 mmol) in dioxane (5 mL) and water (5 mL) was heated to reflux for 15 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 25% acetonitrile/75% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give methyl 3-(8-(6-(3-tert-butylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (60 mg, 12%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.74 (s, 1H), 8.55 (s, 1H), 8.21-8.11 (m, 3H), 7.86 (s, 1H), 7.63-7.47 (m, 2H), 6.27 (d, 1H, J=5.4 Hz), 6.14 (d, 1H, J=7.2 Hz), 3.96 (s, 3H), 3.71-3.68 (m, 1H), 3.48-3.42 (m, 2H), 3.19-3.13 (m, 1H), 2.16-1.98 (m, 2H), 1.82-1.78 (m, 2H). 0.93 (s, 9H). LC-MS: 471, [M+H]+, tR=2.275 min, HPLC: 96.55% at 214 nm, 96.14% at 254 nm, tR=5.449 min.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 15 h under N2
  3. customThe solvent was removed in vacuo
  4. customthe resulting mixture was purified by prep-HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-902a08d941c647018d52f52527cb5ae3
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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