Sodium Carbonate → (1SR,3RS)-3-[3-(2-Chloro-6-fluoro-pyridin-4-yl)-imidazo[1,2-a]pyridin-6-ylamino)-cyclohexanol

HRID 383317Notes

Reaction equation

Br[C:2]1[N:6]2[CH:7]=[C:8]([NH:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH:14]([OH:18])[CH2:13]3)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[Cl:19][C:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[C:22]([F:35])[N:21]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)C.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:19][C:20]1[CH:25]=[C:24]([C:2]2[N:6]3[CH:7]=[C:8]([NH:11][CH:12]4[CH2:17][CH2:16][CH2:15][CH:14]([OH:18])[CH2:13]4)[CH:9]=[CH:10][C:5]3=[N:4][CH:3]=2)[CH:23]=[C:22]([F:35])[N:21]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of 3-trans-RS/RS (3-bromo-imidazo[1,2-a]pyridin-6-ylamino)-cyclohexanol [intermediate J step 2] (1 eq, 0.1 g), 2-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (1.05 eq,82 mg), Na2CO3 (2 eq, 68 mg) in ethanol (2 ml) and water (0.2 ml), under an inert atmosphere of argon is added bis(triphenylphosphine)palladium II chloride (0.1 eq, 0.96 mmol, 22 mg). The reaction mixture is heated at 95° C. for 16 hours. The mixture is diluted with H2O (50 ml) and extracted with EtOAc. The combined organic portions are washed with brine, dried (MgSO4) and concentrated in vacuo. The residue is purified by chromatography on silica eluting with 0-10% MeOH in EtOAc to afford the title compound; [M+H]+=360.

Workup

extractionextracted with EtOAc
washThe combined organic portions are washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe residue is purified by chromatography on silica eluting with 0-10% MeOH in EtOAc

Sources & evidence

ORD record: ord-9f1b0b26650d41d8a312c0a16831ff3e
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367662B2

Reaction notes

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