Tetrahydrofuran → HCID 71280638, compound

HRID 1497926Notes

Reaction equation

HRID 1497926 reaction equation
[N:1]1[CH:2]=[C:3]([C:10]([NH:12][C:13]2[CH:14]=[C:15]([C:20]3[N:24]=[C:23]([CH2:25][CH2:26][C:27]([O:29]C)=[O:28])[O:22][N:21]=3)[CH:16]=[CH:17][C:18]=2[CH3:19])=[O:11])[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[CH2:31]([Mg]Br)[CH3:32].[CH2:35]1COCC1>>[OH:28][C:27]1([CH2:26][CH2:25][C:23]2[O:22][N:21]=[C:20]([C:15]3[CH:16]=[CH:17][C:18]([CH3:19])=[C:13]([NH:12][C:10]([C:3]4[N:4]5[CH:9]=[CH:8][CH:7]=[CH:6][C:5]5=[N:1][CH:2]=4)=[O:11])[CH:14]=3)[N:24]=2)[CH2:32][CH2:31]1.[N:1]1[CH:2]=[C:3]([C:10]([NH:12][C:13]2[CH:14]=[C:15]([C:20]3[N:24]=[C:23]([CH2:25][CH2:26][C:27]([O:29][CH:31]([CH3:32])[CH3:35])=[O:28])[O:22][N:21]=3)[CH:16]=[CH:17][C:18]=2[CH3:19])=[O:11])[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 71280454HCID 71280454, compoundHCID 178418443HCID 178418443, compound

Product 2

HCID 71280638HCID 71280638, compoundHCID 71280740HCID 71280740, compound

Procedure

To a stirring solution of methyl 3-(3-(3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)propanoate (93) (100 mg, 0.25 mmol) in anhydrous THF at −15° C. under argon was added dropwise a solution of ethylmagnesium bromide (247 L, 0.74 mmol). The reaction was stirred at room temperature for 16 hours. The reaction was quenched with saturated NH4Cl. The crude product was extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. The crude product was purified by preparative HPLC to yield both N-(5-(5-(2-(1-hydroxycyclopropyl)ethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (F55a) and isopropyl 3-(3-(3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)propanoate (F55b). 1H NMR for (F55a) (400 MHz, CD2Cl2) δ 9.89 (d, J=6.8 Hz, 1H), 9.81 (s, 1H), 9.56 (s, 1H), 8.21 (s, 1H), 8.19 (d, J=8.0 Hz, 1H), 8.0 (t, J=8.0 Hz, 1H), 7.88 (dd, J=1.6, 7.6 Hz 1H), 7.53 (t, J=7.2 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 3.23 (t, J=7.2 Hz, 2H), 2.47 (s, 3H), 2.12 (t, J=7.2 Hz, 2H), 0.79 (t, J=6.8 Hz, 2H), 0.53 (t, J=6.8 Hz 2H). MS m/z 404.2 (M+1)+.

Workup

  1. customThe reaction was quenched with saturated NH4Cl
  2. extractionThe crude product was extracted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-7119ff967f754c0182f33afe4cd6c45c
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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