Ammonia → 5'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine

HRID 539351Notes

Reaction equation

HRID 539351 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:16][C:15]3([CH2:21][CH2:20][CH:19]([O:22][CH3:23])[CH2:18][CH2:17]3)[C:8]3([NH:12][C:11](=S)[C:10]([CH3:14])=[N:9]3)[C:6]=2[CH:7]=1.[NH3:24].CO>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:16][C:15]3([CH2:21][CH2:20][CH:19]([O:22][CH3:23])[CH2:18][CH2:17]3)[C:8]3([N:12]=[C:11]([NH2:24])[C:10]([CH3:14])=[N:9]3)[C:6]=2[CH:7]=1

Participants

4

Reactant 3

HCID 222Ammonia2×HCID 887Methanol2×HCID 866672755'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazole]-4''(3''H)-thione

Product 1

HCID 679795525'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amineYield 27%

Conditions

Temperature
120 °C

Procedure

A mixture of 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazole]-4″(3″H)-thione (Example 29 Step 3, 365 mg, 0.92 mmol) and 7M ammonia in MeOH (10 mL, 70.00 mmol) was prepared in a microwave vial. The vial was sealed and the reaction was heated at 120° C. for 30 min in a microwave reactor. The mixture was concentrated and the residue was dissolved in 7M ammonia in MeOH (4 mL) and heated once more at 120° C. for 30 min using MW. Again, the mixture was concentrated, 7M ammonia in MeOH (10 mL, 70.00 mmol) was added and the mixture was heated at 120° C. The mixture was concentrated and the crude product was dissolved in 20% MeOH in DCM and filtered through a silica pad and eluted with 20% MeOH in DCM. After concentration of the organic layer, DCM was added to the residue. A solid was formed which was filtered off and washed with DCM, yielding 94 mg of the title compound (27% yield). The mother liquor was concentrated, Et2O was added and the solid was filtered off and dried, yielding a second crop of the title compound (85 mg, 24% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.19 (d, 1 H), 1.43 (m, 3 H), 1.80 (d, 2 H), 1.95 (m, 2 H), 2.20 (s, 3 H), 3.07 (d, 1 H), 3.21 (s, 3 H), 6.68 (d, 1 H), 6.74 (br. s., 2 H), 6.87 (d, 1 H), 7.31 (dd, 1 H); MS (ES+) m/z 379 [M+H]|.

Workup

  1. customwas prepared in a microwave vial
  2. customThe vial was sealed
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue was dissolved in 7M ammonia in MeOH (4 mL)
  5. temperatureheated once more at 120° C. for 30 min
  6. concentrationAgain, the mixture was concentrated
  7. temperaturethe mixture was heated at 120° C
  8. concentrationThe mixture was concentrated
  9. dissolutionthe crude product was dissolved in 20% MeOH in DCM
  10. filtrationfiltered through a silica pad
  11. washeluted with 20% MeOH in DCM
  12. additionAfter concentration of the organic layer, DCM was added to the residue
  13. customA solid was formed which
  14. filtrationwas filtered off
  15. washwashed with DCM

Sources & evidence

ORD record
ord-7b2cea0078a544a6a8823c718168e114
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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