Sodium Carbonate → (S)-methyl 2-methyl-3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

HRID 1755332Notes

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.[CH3:24][C:25]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28].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]>[CH3:24][C:25]1[C:34]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[CH2:22][CH2:21][CH2:20][C@@H:19]4[CH3:23])[N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)=[CH:33][CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28]

Participants

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 (124 mg, 0.38 mmol), methyl 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (124 mg, 0.45 mmol), Pd2(dba)3 (22 mg, 0.038 mmol), X-phos (73 mg, 0.152 mmol) and Na2CO3 (121 mg, 1.14 mmol) in dioxane (10 mL) and water (1 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1) to give (S)-methyl 2-methyl-3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (72 mg, 43%) as a yellow solid. LC-MS: [M+H]+, 443.2, tR=1.880 min.

Workup

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

Sources & evidence

ORD record: ord-66d1542a6b864adfa75339befbdcd0bb
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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