1,2-Dichloroethane → (R)-N-(4-(5-(3 cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyacetamide

HRID 1051054Notes

Reaction equation

HRID 1051054 reaction equation
[OH:1][CH2:2][C:3]([OH:5])=O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:20][C@H:21]1[C:29]2[C:24](=[C:25]([C:30]3[N:34]=[C:33]([C:35]4[CH:36]=[CH:37][C:38]([O:43][CH:44]([CH3:46])[CH3:45])=[C:39]([CH:42]=4)[C:40]#[N:41])[O:32][N:31]=3)[CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22]1>CN(C=O)C.CC(=O)OCC>[C:40]([C:39]1[CH:42]=[C:35]([C:33]2[O:32][N:31]=[C:30]([C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:24]=3[CH2:23][CH2:22][C@H:21]4[NH:20][C:3](=[O:5])[CH2:2][OH:1])[N:34]=2)[CH:36]=[CH:37][C:38]=1[O:43][CH:44]([CH3:46])[CH3:45])#[N:41]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 58344778(R)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile

Product 1

HCID 58344902(R)-N-(4-(5-(3 cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyacetamideYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedure 7. To 2-hydroxyacetic acid (7 mg, 0.08 mmol) in DMF (2 mL) was added HOBt (12 mg, 0.09 mmol) and EDC (17 mg, 0.09 mmol). The reaction mixture was stirred at room temperature for 0.5 h until the acid was fully activated. (R)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 49 (25.0 mg, 0.07 mmol) was added in one portion and the reaction was stirred at room temperature for 12 h. The reaction mixture was diluted with EA and washed with NaHCO3. The combined aqueous layers were back-extracted with EA. The resulting combined organic layers were dried over Na2SO4 and concentrated to a brown oil which was purified by chromatography (MeOH/DCM) to provide 14 mg (48%) of (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxy acetamide 65 as a white solid. LCMS-ESI (m/z) calculated for C22H22N4O4: 418.5. found 419.0 [M+H]+, tR=2.47 min. 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=2.2 Hz, 1H), 8.32 (dd, J=8.9, 2.2 Hz, 1H), 8.08 (d, J=7.6 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 6.76 (d, J=8.6 Hz, 1H), 5.61 (d, J=8.1 Hz, 1H), 4.80 (dt, J=12.2, 6.1 Hz, 1H), 4.20 (s, 2H), 3.49 (m, 1H), 3.23 (dd, J=17.1, 8.5 Hz, 1H), 2.80-2.60 (m, 1H), 1.93 (dd, J=13.0, 8.4 Hz, 1H), 1.47 (t, J=5.6 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 173.11, 171.21, 168.78, 162.78, 144.48, 143.21, 134.11, 133.88, 128.56, 127.42, 126.83, 123.29, 116.76, 115.26, 113.55, 103.90, 72.77, 62.25, 54.00, 33.52, 31.71, 21.72.

Workup

  1. customPrepared
  2. stirringthe reaction was stirred at room temperature for 12 h
  3. washwashed with NaHCO3
  4. extractionThe combined aqueous layers were back-extracted with EA
  5. dry with materialwere dried over Na2SO4
  6. concentrationconcentrated to a brown oil which
  7. customwas purified by chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-eac2877ac0644897991f3dc4ee7fa944
Source dataset
uspto-grants-2016_07
Patent number
US09388147B2

Reaction notes

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