Sodium Carbonate → HCID 136235684, compound

HRID 1755410Notes

Reaction equation

HRID 1755410 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][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=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.[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.[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:28]3[CH:29]=[CH:30][C:25]([OH:24])=[CH:26][CH:27]=3)[CH:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic 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 136235684HCID 136235684, compoundYield 51.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.05 g, 0.15 mmol), 4-hydroxyphenylboronic acid (0.025 g, 4 mmol), Pd(dba)2 (0.02 g, 0.035 mmol), X-Phos (0.02 g, 0.042 mmol) and Na2CO3 (0.032 g, 0.3 mmol) in dioxane/H2O (20 mL/2 mL) was stirred at 95° C. for 18 h under N2. The solvent was removed in vacuo and the residue purified by chromatography (silica gel, petroleum ether/ethyl acetate 3:1) to give 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenol (0.03 g, 51%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.85 (s, 1H), 9.54 (s, 1H), 8.70 (s, 1H), 8.14 (s, 1H), 7.78-7.75 (m, 2H), 7.62 (s, 1H), 7.43 (t, 1H, J=8.0 Hz), 6.91-6.88 (m, 2H), 6.70 (d, 1H, J=7.8 Hz), 6.07 (d, 1H, J=8.1 Hz), 4.22 (brs, 1H), 3.57 (brs, 2H), 2.08-1.98 (m, 3H), 1.69 (brs, 1H), 1.15 (d, 3H, J=6.3 Hz). LC/MS: 387 [M+H]+, 385 [M−H]−, tR=1.59 min. HPLC: 96.77% at 214 nm, 97.82% at 254 nm, tR=6.12 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by chromatography (silica gel, petroleum ether/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-300f766c3e23474db72522e97c852b00
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

Loading…