Sodium Carbonate → 6-(1H-indazol-6-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1755319Notes

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.CC1(C)C(C)(C)OB([C:32]2[CH:40]=[C:39]3[C:35]([CH:36]=[N:37][NH:38]3)=[CH:34][CH:33]=2)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]>[NH:38]1[C:39]2[C:35](=[CH:34][CH:33]=[C:32]([C:2]3[CH:3]=[C:4]([NH:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([N:18]5[CH2:22][CH2:21][CH2:20][CH:19]5[CH3:23])[N:13]=4)[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[N:7]=3)[CH:40]=2)[CH:36]=[N:37]1

Participants

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 (120 mg, 0.365 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (134 mg, 0.547 mmol), Pd2(dba)3 (21 mg, 0.037 mmol), X-phos (70 mg, 0.146 mmol) and Na2CO3 (117 mg, 1.1 mmol) in dioxane (5 mL) and water (0.5 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was first purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1), and then again (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give 6-(1H-indazol-6-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (37 mg, 25%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 13.31 (s, 1H), 9.69 (s, 1H), 8.87 (s, 1H), 8.23 (s, 1H), 8.17 (s, 1H), 8.03 (s, 1H), 7.91 (d, 1H, J=8.4 Hz), 7.69-7.67 (m, 2H), 7.45 (t, 1H, J=7.8 Hz), 6.75 (d, 1H, J=7.8 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.21 (brs, 1H), 3.58 (brs, 1H), 3.45-3.38 (m, 1H), 2.06-1.97 (m, 3H), 1.69 (brs, 1H), 1.11 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 411, tR=1.672 min, HPLC: 95.88% at 214 nm, 98.36% at 254 nm, tR=5.913 min.

Workup

customThe solvent was removed in vacuo
customthe resulting mixture was first purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1)

Sources & evidence

ORD record: ord-12d9158507614887916c9edae467b6a0
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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