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

HRID 1965103Notes

Reaction equation

HRID 1965103 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(3 H)-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% (0.1M 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, 1 H), 7.27 (d, 1 H), 6.68 (d, 1 H), 6.65 (br. s, 1 H), 3.65 (m, 2 H), 3.46 (m, 1 H), 3.38 (m, 1 H), 3.15 (m, 1 H), 3.00 (m, 1 H), 2.18 (s, 3 H), 1.66 (td, 1 H), 1.19 (m, 3 H); 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% (0.1M NH3 in MeOH) in DCM

Sources & evidence

ORD record
ord-d09c1d40ddb341e08223077fa8f6e8a2
Source dataset
uspto-grants-2013_04
Patent number
US08415483B2

Reaction notes

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