Acetyl chloride → HCID 67006065, compound

HRID 563348Notes

Reaction equation

HRID 563348 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C@H:13]([NH:24][C:25]3[C:26]([CH3:34])=[CH:27][C:28]([Cl:33])=[C:29]([CH:32]=3)[C:30]#[N:31])[C@@H:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH3:15])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C:35](Cl)(=[O:37])[CH3:36]>C(Cl)Cl.N1C=CC=CC=1>[Si:17]([O:16][C@@H:14]([CH3:15])[C@H:13]([C:11]1[O:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:35](=[O:37])[CH3:36])=[CH:7][CH:6]=2)=[N:9][N:10]=1)[NH:24][C:25]1[CH:32]=[C:29]([C:30]#[N:31])[C:28]([Cl:33])=[CH:27][C:26]=1[CH3:34])([C:20]([CH3:23])([CH3:21])[CH3:22])([CH3:19])[CH3:18]

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 67005939HCID 67005939, compound2×

Product 1

HCID 67006065HCID 67006065, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a pre-cooled (0° C.) solution of 5-((1R,2S)-1-(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-4-methylbenzonitrile (intermediate 77d) (200 mg, 0.40 mmol) in CH2Cl2 (4.0 mL) and pyridine (1.04 mL) was added, portion wise, acetyl chloride (0.14 mL, 2.0 mmol). Upon complete addition the reaction mixture was warmed slowly to room temperature and stirred for 23 h. The reaction mixture was then cooled to 0° C. and quenched with 10% ap HCl (5 mL) then H2O (15 mL) was added. The solution was extracted with CH2Cl2 (2×30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to provide an orange oil, which was used without further purification (199 mg, 92%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 8.11 (d, J=8.4 Hz, 2H), 7.87 (d, J=8.6 Hz, 2H), 7.80 (br s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 5.57 (d, J=8.9 Hz, 1H), 4.99 (dd, J=1.8, 8.9 Hz, 1H), 4.76-4.68 (m, 1H), 2.58 (s, 3H), 2.44 (s, 3H), 1.62 (d, J=6.3 Hz, 3H), 1.07 (s, 9H), 0.27 (s, 3H), 0.00 (s, 3H).

Workup

  1. additionwas added
  2. additionUpon complete addition the reaction mixture
  3. temperatureThe reaction mixture was then cooled to 0° C.
  4. customquenched with 10% ap HCl (5 mL)
  5. additionH2O (15 mL) was added
  6. extractionThe solution was extracted with CH2Cl2 (2×30 mL)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto provide an orange oil, which
  11. customwas used without further purification (199 mg, 92%)

Sources & evidence

ORD record
ord-aef900013d424ad997a40407334a4280
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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