Ammonia → HCID 67979367, compound

HRID 539381Notes

Reaction equation

HRID 539381 reaction equation
[Br:1][C:2]1[CH:25]=[C:24]2[C:5]([CH2:6][C:7]3([C:17]42[NH:21][C:20](=S)[C:19]([CH3:23])=[N:18]4)[CH2:12][CH2:11][CH:10]([C:13]([F:16])([F:15])[F:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[NH3:26]>>[Br:1][C:2]1[CH:25]=[C:24]2[C:5]([CH2:6][C:7]3([C:17]42[N:21]=[C:20]([NH2:26])[C:19]([CH3:23])=[N:18]4)[CH2:12][CH2:11][CH:10]([C:13]([F:16])([F:15])[F:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 222Ammonia2×HCID 86692167HCID 86692167, compound

Product 1

HCID 67979367HCID 67979367, compoundYield 21.5%

Conditions

Temperature
110 °C

Procedure

6′-Bromo-5″-methyl-4-(trifluoromethyl)-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazole]-4″(3″H)-thione (Example 124 Step 2, 40 mg, 0.09 mmol) was dissolved in ammonia (7 M in MeOH) (2 mL, 14.0 mmol) in a microwave vial. The vial was capped, and heated to 110° C. for min in a microwave reactor. The solution was concentrated, and the residue dissolved in ammonia (7 M in MeOH) (2 mL, 14.0 mmol) and heated to 110° C. in a microwave reactor. This cycle (concentration, addition of ammonia and heating) was repeated until all starting material was converted to product (6 times). The reaction mixture was cooled to r.t., concentrated in vacuo and purified by preparative chromatography to give the title compound (8 mg, 21% yield): 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.19-1.38 (m, 4 H) 1.42-1.59 (m, 3 H) 1.84-1.92 (m, 1 H) 1.98 (m, 1 H) 2.20 (s, 3 H) 2.76-2.94 (m, 2 H) 6.55-6.62 (m, 3 H) 7.22 (m, 1 H) 7.34 (m, 1 H); MS (APCI+) 416 [M+H]+.

Workup

  1. customThe vial was capped
  2. concentrationThe solution was concentrated
  3. temperatureheated to 110° C. in a microwave reactor
  4. concentrationThis cycle (concentration, addition of ammonia and heating)
  5. temperatureThe reaction mixture was cooled to r.t.
  6. concentrationconcentrated in vacuo
  7. custompurified by preparative chromatography

Sources & evidence

ORD record
ord-668f7ae0654e49e8b2994f19c68077ef
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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