Trichloroacetyl isocyanate → Urea, [8-(4-cyano-1-naphthalenyl)-8-azabicyclo[3.2.1]oct-3-yl]-

HRID 916329Notes

Reaction equation

HRID 916329 reaction equation
Cl.[NH2:2][CH:3]1[CH2:9][CH:8]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]([C:21]#[N:22])=[CH:13][CH:12]=3)[CH:5]([CH2:6][CH2:7]2)[CH2:4]1.ClC(Cl)(Cl)[C:25]([N:27]=C=O)=[O:26]>O1CCCC1>[C:21]([C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([N:10]2[CH:8]3[CH2:7][CH2:6][CH:5]2[CH2:4][CH:3]([NH:2][C:25]([NH2:27])=[O:26])[CH2:9]3)=[CH:12][CH:13]=1)#[N:22]

Participants

4

Reactant 2

HCID 76400Trichloroacetyl isocyanateHCID 1317266004-(3-Amino-8-azabicyclo[3.2.1]oct-8-yl)naphthalene-1-carbonitrile, hydrochloride

Product 1

HCID 11515269Urea, [8-(4-cyano-1-naphthalenyl)-8-azabicyclo[3.2.1]oct-3-yl]-Yield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The amine 165RL21 (40 mg, 0.144 mmol) was dissolved in tetrahydrofuran (1 mL) and cooled to 0° C. Trichloroacetyl isocyanate (0.019 mL) was added and the solution was left to warm to rt and stirring was continued for 30 minutes. The mixture was concentrated and the residue was dissolved in methanol (1 mL). 2 M NaOH (1 mL) was added, and the mixture was heated to 70° C. for 1 hour. Then, water (20 mL) was added and methanol was removed by evaporation in vacuo. The aqueous phase was extracted with dichloromethane (2×20 mL), and the combined organic phases were dried over sodium sulfate, filtered and evaporated. The residue was purified by preparative TLC (0-5% methanol in dichloromethane) to give the title compound (24 mg, 52% yield) as a white solid.

Workup

  1. waitthe solution was left
  2. temperatureto warm to rt
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue was dissolved in methanol (1 mL)
  5. addition2 M NaOH (1 mL) was added
  6. temperaturethe mixture was heated to 70° C. for 1 hour
  7. additionThen, water (20 mL) was added
  8. custommethanol was removed by evaporation in vacuo
  9. extractionThe aqueous phase was extracted with dichloromethane (2×20 mL)
  10. dry with materialthe combined organic phases were dried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue was purified by preparative TLC (0-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-96125bc080a845e78418d8fdb48c03e1
Source dataset
uspto-grants-2007_09
Patent number
US07268232B2

Reaction notes

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