Acetyl chloride → 1306761-08-9

HRID 1051082Notes

Reaction equation

HRID 1051082 reaction equation
Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[N:16]=[C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])[O:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[C:29](Cl)(=[O:31])[CH3:30]>C(Cl)Cl>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[O:14][N:13]=[C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH2:5][CH2:4][C@@H:3]4[NH:2][C:29](=[O:31])[CH3:30])[N:16]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 67313311HCID 67313311, compound

Product 1

HCID 529391661306761-08-9Yield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Prepared using General Procedure 14: To a stirred solution of (S)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride 50 (500 mg, 1.26 mmol) in DCM (5 mL) was added TEA (527 μL, 378 mmol). The reaction was cooled to 0° C. and acetyl chloride (135 μL, 1.89 mmol) was added. The reaction was stirred at room temperature for 18 h. The solvent was removed under reduced pressure. The residue was diluted with DCM (100 mL) and washed successively with saturated NH4Cl and NaHCO3. The organic layers were dried over MgSO4, filtered and concentrated to crude product. The crude product was recrystallized from hot ethanol (75 mL) to afford 420 mg (83%) of (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide 139 as off-white crystals. LCMS-ESI (m/z) calculated for C23H22N4O3: 402.2. found 403.1 [M+H]+, tR=8.77 min (Method 2). Elemental Analysis determined for C23H22N4O3; C calculated=68.64%. found=68.54%. H calculated=5.51%. found=5.36%. N calculated=13.92%. found=13.85%. 1H NMR (400 MHz, DMSO) δ 8.58 (d, J=2.2 Hz, 1H), 8.47 (dd, J=9.0, 2.3 Hz, 1H), 8.39 (d, J=8.2 Hz, 1H) 8.08 (t, J=4.2 Hz, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.57-7.47 (m, 2H), 5.45-5.39 (m, 1H), 5.20-4.97 (m, 1H), 3.51-3.42 (m, 1H), 3.25-3.00 (m, 1H), 2.55-2.50 (m, 1H), 1.96 (s, 3H), 1.94-1.87 (m, 1H), 1.45 (d, J=6.0 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 173.14, 169.85, 168.85, 162.79, 144.91, 143.26, 134.16, 133.89, 128.49, 127.40, 126.86, 123.29, 116.82, 115.29, 113.56, 103.97, 72.77, 54.56, 33.67, 31.70, 23.50, 21.75. Chiral HPLC: (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide was eluted using 10% i-PrOH in hexanes plus 0.3% DEA: >99.9% ee, tR=15.09 min. (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide 138 was prepared in an analogous fashion from (R)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 49: >99.9% ee, tR for (R)-enantiomer=16.44 min.

Workup

  1. customPrepared
  2. customThe solvent was removed under reduced pressure
  3. additionThe residue was diluted with DCM (100 mL)
  4. washwashed successively with saturated NH4Cl and NaHCO3
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to crude product
  8. customThe crude product was recrystallized from hot ethanol (75 mL)

Sources & evidence

ORD record
ord-ff4c1832d6574578a8c65c31b1b4dd04
Source dataset
uspto-grants-2016_07
Patent number
US09388147B2

Reaction notes

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