Sodium Chloride → 4-(5-(4-isopropoxy-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ol

HRID 1258767Notes

Reaction equation

HRID 1258767 reaction equation
[CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][C:6]=1[C:14]([F:17])([F:16])[F:15])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[OH:39][C:40]1(O)[C:48]2[CH:47]=[CH:46][CH:45]=[C:44]([C:49](=[NH:51])[NH2:50])[C:43]=2[CH2:42][CH2:41]1.[Na+].[Cl-]>CN(C=O)C>[CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]2[O:11][N:51]=[C:49]([C:44]3[CH:45]=[CH:46][CH:47]=[C:48]4[C:43]=3[CH2:42][CH2:41][CH:40]4[OH:39])[N:50]=2)=[CH:7][C:6]=1[C:14]([F:17])([F:16])[F:15])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 225977674-Isopropoxy-3-(trifluoromethyl)benzoic acidHCID 67198250dihydroxy-2,3-dihydro-1H-indene-4-carboximidamide

Product 1

HCID 251105044-(5-(4-isopropoxy-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-olYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

In a microwave vial, a stirring solution of 4-isopropoxy-3-(trifluoromethyl)benzoic acid (700 mg, 2.82 mmol) in DMF was treated with HOBt (495 mg, 3.67 mmol) and EDCI (702 mg, 3.67 mmol) at room temperature. The reaction was stirred for 20 min followed by addition, in a single portion, of NJ-dihydroxy-2,3-dihydro-1H-indene-4-carboximidamide (650 mg, 3.38 mmol). The reaction was stirred for additional 30 min at room temperature and then heated to 130° C. for 35 min in the initiator. The reaction was diluted using a saturated solution of NaCl and extracted with EtOAc (100 ml×3). The organic phase was dried over Na2SO4 anhydrous and concentrated under reduced pressure. The product was purified by column chromatography using CH2Cl2:MeOH (9:1) to offer the product as white solid in 68% yield (780 mg). 1H NMR (300 MHz, CDCl3-CH3OD): δ 8.38 (d, J=1.8 Hz, 1H), 8.28 (dd, J1=2.4 Hz, J2=8.7 Hz, 1H), 8.06 (d, J=7.8 Hz, 1H), 7.55 (d, J=7.5 1H), 7.7.37 (t, J=7.5 Hz, 1H), 7.11 (dd, J1=2.4 Hz, J2=9.0 Hz, 1H), 5.24 (t, J=6.3 Hz, 1H), 4.20 (q, J=6.9 Hz, 1H), 3.48-3.40 (m, 1H), 3.19-3.09 (m, 1H), 2.57-2.46 (m, 1H), 2.04-1.92 (m, 1H), 1.46 (t, J=6.9 Hz, 3H), 1.39 (d, J=6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3-CH3OD): δ 169.05, 158.85, 146.82, 143.33, 133.55, 128.79, 127.41, 127.22, 116.23, 113.38, 104.88, 65.27, 35.55, 31.44, 21.87, 14.55. MS (EI) m/z 405 (M+), HRMS (EI) for C21H19N2O3 (M+): calcd 405.1420, found 405.1424.

Workup

  1. stirringThe reaction was stirred for additional 30 min at room temperature
  2. additionThe reaction was diluted
  3. extractionextracted with EtOAc (100 ml×3)
  4. dry with materialThe organic phase was dried over Na2SO4 anhydrous
  5. concentrationconcentrated under reduced pressure
  6. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-7b767750d29942f0b934d881c1a0283a
Source dataset
uspto-grants-2013_06
Patent number
US08466183B2

Reaction notes

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