Ethylene Glycol → HCID 71281216, compound

HRID 1497920Notes

Reaction equation

CS(OC[C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13]([C:16](=[O:36])[NH:17][C:18]3[CH:23]=[C:22]([C:24]4[N:28]=[C:27]([CH:29]5[CH2:32][C:31]([F:34])([F:33])[CH2:30]5)[O:26][N:25]=4)[CH:21]=[CH:20][C:19]=3[CH3:35])=[CH:14][N:15]=2)[CH:12]=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[CH2:43]([OH:46])[CH2:44][OH:45]>>[F:34][C:31]1([F:33])[CH2:30][CH:29]([C:27]2[O:26][N:25]=[C:24]([C:22]3[CH:21]=[CH:20][C:19]([CH3:35])=[C:18]([NH:17][C:16]([C:13]4[N:11]5[CH:12]=[C:7]([O:45][CH2:44][CH2:43][OH:46])[CH:8]=[CH:9][C:10]5=[N:15][CH:14]=4)=[O:36])[CH:23]=3)[N:28]=2)[CH2:32]1

Participants

Reactant 3

HCID 174Ethylene Glycol

HCID 11430Potassium Carbonate

HCID 86677534HCID 86677534, compound

Product 1

HCID 71281216HCID 71281216, compound

Conditions

Temperature: 80 °C

Procedure

N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(hydroxymethyl)imidazo[1,2-a]pyridine-3-carboxamide (F37) (0125 mg, 0.285 mmol) was dissolved in DCM (1 mL) and DIEA (0.854 mmol). MsCl (0.57 mmol) was added dropwise. After 15 minutes at room temperature the solvent was removed. MeOH (5 mL) and water (10 mL) were added to the residue. After sonication, most of the MeOH was removed from the mixture. Solid product was filtered and dried under vacuum to give the crude mesylate, which was used in the next step without purification. MS m/z 518.0 (M+1)+. A mixture of (3-((5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)methyl methanesulfonate (10.4 mg, 0.02 mmol) and K2CO3(8.3 mg, 0.06 mmol) in ethane-1,2-diol (0.5 mL) was heated at 80° C. for 20 minutes. The reaction mixture was purified by preparative HPLC to afford N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-3-carboxamide (F38). 1H NMR (400 MHz, CDCl3) δ 9.56 (m, 1H), 8.60 (d, J=1.5 Hz, 1H), 8.21 (s, 1H), 7.89 (dd, J=1.7, 7.9 Hz, 1H), 7.77 (d, J=9.2 Hz, 1H), 7.60 (s, 1H), 7.50 (dd, J=1.7, 9.2 Hz, 1H), 7.42 (d, J=7.9 Hz, 1H), 4.65 (s, 2H), 3.82 (s, 2H), 3.73-3.61 (m, 3H), 3.15 (m, 4H), 2.46 (s, 3H), 2.04 (s, 1H). MS m/z 484.2 (M+1)+.

Workup

customwas used in the next step without purification
customThe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-a502d8dc00594d9a92ee42cbbf1b43a6
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199981B2

Reaction notes

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