Hydrochloric Acid → HCID 131735384, compound

HRID 629822Notes

Reaction equation

HRID 629822 reaction equation
C([NH:9][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:19][C@H:18]([CH3:20])[O:17][CH2:16][C@:14]2([C:21]2[S:22][CH:23]=[C:24]([NH:26][C:27]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[CH:31][N:30]=3)=[O:28])[N:25]=2)[N:15]=1)(=O)C1C=CC=CC=1.[ClH:39]>C1(C)C=CC=CC=1.ClCCl>[ClH:39].[NH2:9][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:19][C@H:18]([CH3:20])[O:17][CH2:16][C@:14]2([C:21]2[S:22][CH:23]=[C:24]([NH:26][C:27]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:37])[F:38])=[CH:31][N:30]=3)=[O:28])[N:25]=2)[N:15]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 118435422HCID 118435422, compound

Product 1

HCID 131735384HCID 131735384, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
35 °C

Procedure

SiliCycle, SiliaMetS® Diamine (4.72 g, 5.36 mmol) was added to a solution of C9 (1.00 g, 1.79 mmol) in toluene (10 mL), and the reaction mixture was heated at reflux overnight. After being cooled to 35° C., the reaction mixture was diluted with dichloromethane (10 mL), stirred for 10 minutes at 35° C., and filtered through diatomaceous earth to remove the SiliCycle reagent. The filter pad was rinsed with dichloromethane and the combined filtrates were heated to reflux and displaced with isopropyl acetate (4×10 mL) to a final volume of 15 mL. This mixture was heated to 50° C., treated with concentrated hydrochloric acid (0.17 mL, 2.0 mmol), and subsequently cooled to 0° C. to 5° C. and allowed to granulate for 1 hour. The solid was collected via filtration and washed with cold propan-2-yl acetate to afford the product as a solid. This material was crystalline by powder X-ray diffraction analysis. Yield: 0.67 g, 1.4 mmol, 78%. 1H NMR (400 MHz, DMSO-d6) δ 11.30 (br s, 1H), 10.73 (s, 1H), 9.6-9.9 (v br s, 1H), 8.6-8.9 (v br s, 1H), 8.63 (d, J=2.7 Hz, 1H), 8.24 (d, J=8.6 Hz, 1H), 7.93 (dd, J=8.7, 2.8 Hz, 1H), 7.84 (s, 1H), 7.51 (t, JHF=72.8 Hz, 1H), 3.96 (AB quartet, JAB=12.2 Hz, ΔνAB=62.6 Hz, 2H), 3.75-3.85 (m, 1H), 3.02-3.11 (m, 3H), 1.73-1.82 (m, 1H), 1.39-1.52 (m, 1H), 1.21 (d, J=6.2 Hz, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux overnight
  3. filtrationfiltered through diatomaceous earth
  4. customto remove the SiliCycle reagent
  5. washThe filter pad was rinsed with dichloromethane
  6. temperaturethe combined filtrates were heated
  7. temperatureto reflux
  8. temperatureThis mixture was heated to 50° C.
  9. temperaturesubsequently cooled to 0° C. to 5° C.
  10. waitto granulate for 1 hour
  11. filtrationThe solid was collected via filtration
  12. washwashed with cold propan-2-yl acetate

Sources & evidence

ORD record
ord-ae9dc75db6cf4ab7ac4643390fcbfae4
Source dataset
uspto-grants-2016_04
Patent number
US09315520B2

Reaction notes

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