Sodium hydride → HCID 52939655, compound

HRID 1809534Notes

Reaction equation

HRID 1809534 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C@H:22]4[N:27]([CH2:35][CH2:36][OH:37])[C:28](=O)[O:29]C(C)(C)C)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[H-].[Na+]>CN(C=O)C.CC(=O)OCC>[CH:10]([O:9][C:8]1[CH:7]=[CH:6][C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C@H:22]4[N:27]3[CH2:35][CH2:36][O:37][C:28]3=[O:29])[N:14]=2)=[CH:4][C:3]=1[C:1]#[N:2])([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 71241362HCID 71241362, compound

Product 1

HCID 52939655HCID 52939655, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (R)-tert-butyl (4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)(2-hydroxyethyl)carbamate INT-22 in DMF (1 mL) was added NaH (6 mg, 0.15 mmol, of a 60% solution in mineral oil). After stirring for 20 h, the reaction mixture was diluted with EA and washed with NaHCO3. The combined aqueous extracts were back-extracted with EA. The combined organic extracts were dried over Na2SO4, concentrated, and purified by column chromatography (EA/hexanes) to provide 11.9 mg (29%) of (R)-2-isopropoxy-5-(3-(1-(2-oxooxazolidin-3-yl)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)benzonitrile 154. LCMS-ESI (m/z) calculated for C22H22N4O4: 430.5; found 431.1 [M+H]+, tR=3.72 min. 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J=2.2 Hz, 1H), 8.34 (dd, J=8.9, 2.2 Hz, 1H), 8.14 (t, J=4.4 Hz, 1H), 7.42 (m, 2H), 7.13 (d, J=9.0 Hz, 1H), 5.72-5.57 (m, 1H), 4.80 (dt, J=12.2, 6.1 Hz, 1H), 4.35 (qt, J=15.7, 7.8 Hz, 2H), 3.56-3.39 (m, 2H), 3.25 (dtd, J=24.4, 8.6, 7.1 Hz, 2H), 2.65-2.48 (m, 1H), 2.10 (ddt, J=13.7, 9.0, 7.1 Hz, 1H), 1.48 (d, J=6.1 Hz, 6H). Compound 155 was made in an analogous fashion.

Workup

  1. washwashed with NaHCO3
  2. extractionThe combined aqueous extracts were back-extracted with EA
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by column chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-2ab95be6bd7a4d88963130b695c410cf
Source dataset
uspto-grants-2013_01
Patent number
US08362048B2

Reaction notes

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