Ammonia → 6'-Bromo-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

HRID 1770939Notes

Reaction equation

HRID 1770939 reaction equation
[Br:1][C:2]1[CH:23]=[C:22]2[C:5]([CH2:6][C:7]3([C:15]42[NH:19][C:18](=S)[C:17]([CH3:21])=[N:16]4)[CH2:12][CH2:11][CH:10]([O:13][CH3:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[NH3:24]>>[Br:1][C:2]1[CH:23]=[C:22]2[C:5]([CH2:6][C:7]3([C:15]42[N:19]=[C:18]([NH2:24])[C:17]([CH3:21])=[N:16]4)[CH2:12][CH2:11][CH:10]([O:13][CH3:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 222Ammonia6×HCID 866672716'-Bromo-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

Product 1

HCID 573851176'-Bromo-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amineYield 82.2%

Conditions

Temperature
120 °C

Procedure

6′-Bromo-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazole]-4″(3″H)-thione (Example 19 Step 3, 0.936 g, 2.38 mmol) was taken up in ammonia (7M in MeOH, 10 mL, 70.00 mmol) and the resulting mixture was bubbled with argon and then heated in the microwave reactor at 120° C. for 1 h. The solvent was evaporated. Ammonia (7M in MeOH, 6 mL, 42 mmol) was added and the reaction was bubbled with argon and heated again using MW for 60 min at 120° C. The solvent was evaporated and ammonia (7M in MeOH, 10 mL, 70 mmol) was added. The reaction was bubbled with argon and then heated using MW for 2 h at 120° C. The solvent was evaporated and ammonia (7M in MeOH, 15 mL, 105 mmol) was added and the reaction was heated again for 2 h at 120° C. The solvent was evaporated and ammonia (7M in MeOH, 15 mL, 105 mmol) was added and the reaction was heated again for 2 h at 120° C. The solvent was evaporated and ammonia (7M in MeOH, 20 mL, 140 mmol) was added. The reaction was heated again using MW for 1 h at 120° C. The solvent was evaporated and the resulting residue was taken up in DCM (60 mL) and brine (×2) and poured into a phase separator. The organic phase was dried with MgSO4, filtered and evaporated to give the title compound (0.736 g, 82% yield) as a mixture of isomers: 1H NMR (500 MHz, CDCl3) δ ppm 1.09 (td, 1H), 1.27-1.49 (m, 3H), 1.62-1.74 (m, 2H), 1.93-2.01 (m, 2H), 2.37 (s, 3H), 3.04-3.18 (m, 3H), 3.34 (s, 3H), 6.90 (d, 1H), 7.20 (d, 1H), 7.38 (dd, 1H); MS (MM-ES+APCI)+m/z 376 [M+H]+.

Workup

  1. customthe resulting mixture was bubbled with argon
  2. customThe solvent was evaporated
  3. customthe reaction was bubbled with argon
  4. temperatureheated again using MW for 60 min at 120° C
  5. customThe solvent was evaporated
  6. customThe reaction was bubbled with argon
  7. temperatureheated
  8. customfor 2 h
  9. customat 120° C
  10. customThe solvent was evaporated
  11. temperaturethe reaction was heated again for 2 h at 120° C
  12. customThe solvent was evaporated
  13. temperaturethe reaction was heated again for 2 h at 120° C
  14. customThe solvent was evaporated
  15. temperatureThe reaction was heated again using MW for 1 h at 120° C
  16. customThe solvent was evaporated
  17. additionbrine (×2) and poured into a phase separator
  18. dry with materialThe organic phase was dried with MgSO4
  19. filtrationfiltered
  20. customevaporated

Sources & evidence

ORD record
ord-eb76d492976244ee91f6006b7bf03363
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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