2-Fluoroethanol → HCID 71505169, compound

HRID 1497945Notes

Reaction equation

HRID 1497945 reaction equation
[F:1][C:2]1([F:32])[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[C:26]([CH2:29][OH:30])[CH:27]=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.C([O-])([O-])=O.[K+].[K+].[F:53][CH2:54][CH2:55]O>C(Cl)Cl>[F:32][C:2]1([F:1])[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[C:26]([CH2:29][O:30][CH2:55][CH2:54][F:53])[CH:27]=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1

Participants

7

Reactant 5

HCID 97372-FluoroethanolHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 71280658HCID 71280658, compound

Product 1

HCID 71505169HCID 71505169, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(hydroxymethyl)imidazo[1,2-a]pyridine-3-carboxamide (F159) (95 mg, 0.216 mmol) was dissolved in DCM (1 mL) and DIEA (0.65 mmol). MsCl (0.65 mmol) was added dropwise and the resulting mixture was stirred for 15 minutes at room temperature. The reaction mixture was subjected to aqueous workup, extracted with DCM (2 mL), dried over Na2SO4 and concentrated to give a crude which was dissolved in 0.8 mL of 2-fluoroethanol followed by addition of K2CO3(90 mg, 0.65 mmol). The resulting mixture was heated at 120° C. for 20 minutes. The reaction mixture was subjected to standard aqueous workup and purified by silica chromatography to yield N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-((2-fluoroethoxy)methyl)imidazo[1,2-a]pyridine-3-carboxamide (F176). 1H NMR (400 MHz, CDCl3) δ 9.56 (s, 1H), 8.60 (d, J=1.6, 1H), 8.21 (s, 1H), 7.89 (dd, J=1.7, 7.9, 1H), 7.77 (d, J=9.2, 1H), 7.62 (s, 1H), 7.53 (dd, J=1.7, 9.2, 1H), 7.42 (d, J=8.1, 1H), 4.72-4.64 (m, 3H), 4.59-4.52 (m, 1H), 3.86-3.79 (m, 1H), 3.79-3.73 (m, 1H), 3.68 (m, 1H), 3.16 (m, 4H), 2.47 (s, 3H). MS m/z 486.1 (M+1)+.

Workup

  1. extractionextracted with DCM (2 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto give a crude which
  5. temperatureThe resulting mixture was heated at 120° C. for 20 minutes
  6. custompurified by silica chromatography

Sources & evidence

ORD record
ord-2d3ae82d97c1449dacdb1ccf58b4fed0
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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