Cesium carbonate → N-{6-[(2s)-2-Methylpyrrolidin-1-Yl]pyridin-2-Yl}-6-Phenylimidazo[1,2-B]pyridazin-8-Amine

HRID 1755357Notes

Reaction equation

HRID 1755357 reaction equation
Br[C:2]1[C:3]2[N:4]([CH:14]=[CH:15][N:16]=2)[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1.[CH3:17][C@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[C:23]1[N:28]=[C:27]([NH2:29])[CH:26]=[CH:25][CH:24]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:17][C@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[C:23]1[N:28]=[C:27]([NH:29][C:2]2[C:3]3[N:4]([CH:14]=[CH:15][N:16]=3)[N:5]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:7]=2)[CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 717440288-Bromo-6-phenylimidazo[1,2-B]pyridazineHCID 86674492(S)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine

Product 1

HCID 71525988N-{6-[(2s)-2-Methylpyrrolidin-1-Yl]pyridin-2-Yl}-6-Phenylimidazo[1,2-B]pyridazin-8-AmineYield 25%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 8-bromo-6-phenylimidazo[1,2-b]pyridazine (0.15 g, 0.55 mmol), (S)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (0.107 g, 0.61 mmol), Pd2(dba)3 (32 mg, 0.055 mmol), BINAP (68 mg, 0.11 mmol) and Cs2CO3 (0.54 g, 1.65 mmol) in dioxane (20 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated and the residue purified by chromatography (silica gel, 20 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford (S)—N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine (51 mg, 25%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.83 (s, 1H), 7.99 (s, 1H), 7.95-7.91 (m, 2H), 7.59 (s, 1H), 7.51-7.40 (m, 4 h), 6.29 (d, 1H, J=7.5 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.28-4.24 (m, 1H), 3.64-3.60 (m, 1H), 3.48-3.40 (m, 1H), 2.18-2.10 (m, 3H), 1.78-1.75 (m, 1H), 1.19 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 371, tR=2.015 min, HPLC: 99.09% at 214 nm, 99.69% at 254 nm, tR=4.691 min.

Workup

  1. concentrationthen concentrated
  2. customthe residue purified by chromatography (silica gel, 20 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15)

Sources & evidence

ORD record
ord-7be2678c51d643ad8710a1a7ec45752d
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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