Sodium Carbonate → (S)-6-(benzo[d]thiazol-6-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1755368Notes

Reaction equation

HRID 1755368 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][C@@H: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]=[CH:39][C:35]3[N:36]=[CH:37][S:38][C:34]=3[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]>[S:38]1[C:34]2[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][C@@H:19]5[CH3:23])[N:13]=4)[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[N:7]=3)[CH:40]=[CH:39][C:35]=2[N:36]=[CH:37]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467398066-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzothiazoleHCID 86682714(S)-6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 71526082(S)-6-(benzo[d]thiazol-6-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineYield 51%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.15 g, 0.456 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (0.119 g, 0.456 mmol), Pd2(dba)3 (0.052 g, 0.09 mmol), X-phos (0.087 g, 0.18 mmol) and Na2CO3 (0.145 g, 1.368 mmol) in dioxane (20 mL) and water (5 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 15 g, 200-300 mesh, ethyl acetate:petroleum ether=1:5) to afford (S)-6-(benzo[d]thiazol-6-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (58 mg, 51%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.71 (s, 1H), 9.49 (s, 1H), 8.91 (s, 1H), 8.69 (s, 1H), 8.23-8.08 (m, 3H), 7.66 (s, 1H), 7.43 (t, 1H, J=7.8 Hz), 6.74 (d, 1H, J=7.8 Hz), 6.06 (d, 1H, J=7.8 Hz), 4.26-4.23 (m, 1H), 3.59-3.55 (m, 1H), 3.44-3.40 (m, 1H), 2.08-1.98 (m, 3H), 1.69-1.66 (m, 1H), 1.09 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 428, tR=1.997 min, HPLC: 95.07% at 214 nm, 98.34% at 254 nm, tR=4.349 min.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was purified by chromatography (silica gel, 15 g, 200-300 mesh, ethyl acetate:petroleum ether=1:5)

Sources & evidence

ORD record
ord-32cbe985f905476db03cb275caa36a94
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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