Ammonia → 6'-Bromo-5-methyl-2'',3'',5'',6''-tetrahydro-3'H-dispiro[imidazole-2,1'-indene-2',4''-pyran]-4-amine

HRID 1770946Notes

Reaction equation

HRID 1770946 reaction equation
[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([CH2:6][C:7]3([C:13]42[NH:19][C:18](=S)[C:17]([CH3:21])=[N:16]4)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[NH3:22]>>[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([CH2:6][C:7]3([C:13]42[N:19]=[C:18]([NH2:22])[C:17]([CH3:21])=[N:16]4)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 222Ammonia2×HCID 866672736'-Bromo-5-methyl-2'',3'',5'',6''-tetrahydro-3'H-dispiro[imidazole-2,1'-indene-2',4''-pyran]-4(3H)-thione

Product 1

HCID 573858806'-Bromo-5-methyl-2'',3'',5'',6''-tetrahydro-3'H-dispiro[imidazole-2,1'-indene-2',4''-pyran]-4-amineYield 75%

Conditions

Temperature
120 °C

Procedure

6′-Bromo-5-methyl-2″,3″,5″,6″-tetrahydro-3′H-dispiro[imidazole-2,1′-indene-2′,4″-pyran]-4(3H)-thione (Example 25 Step 3, 415 mg, 1.14 mmol) was taken up in NH3 (7M in MeOH, 13 mL, 91 mmol) and the resulting mixture was heated in a microwave reactor at 120° C. for 2×1 h. The mixture was concentrated and the resulting residue was taken up in NH3 (7M in MeOH, 13 mL, 91 mmol) and then heated again for 1 h at 120° C. The mixture was concentrated and the resulting residue was taken up in DCM (10 mL) and sat. aq. NaHCO3 (5 mL) and poured into a phase separator. The organic layer was collected, concentrated and purified on a silica gel column eluted with 0-10% (0.1 M NH3 in MeOH) in DCM to give 295 mg (75% yield) of the title compound: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.36 (dd, 1H), 7.27 (d, 1H), 6.68 (d, 1H), 6.65 (br. s, 1H), 3.65 (m, 2H), 3.46 (m, 1H), 3.38 (m, 1H), 3.15 (m, 1H), 3.00 (m, 1H), 2.18 (s, 3H), 1.66 (td, 1H), 1.19 (m, 3H); MS (ES+) m/z 348[M+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. temperatureheated again for 1 h at 120° C
  3. concentrationThe mixture was concentrated
  4. additionsat. aq. NaHCO3 (5 mL) and poured into a phase separator
  5. customThe organic layer was collected
  6. concentrationconcentrated
  7. custompurified on a silica gel column
  8. washeluted with 0-10% (0.1 M NH3 in MeOH) in DCM

Sources & evidence

ORD record
ord-d929c02e721b4032885b2d9b35ed5677
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

Loading…