4-(4-hydrazinylphenyl)-4H-1,2,4-triazole → HCID 9888722, compound

HRID 1872026Notes

Reaction equation

HRID 1872026 reaction equation
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:11]=[CH:10][C:9]([NH:12]N)=[CH:8][CH:7]=2)[CH:5]=1.[CH2:14]([N:21]1[CH2:28][CH:27]2[CH:23]([CH2:24][N:25]([CH2:29][CH2:30][CH2:31][CH2:32][CH:33](OC)OC)[CH2:26]2)[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>S(=O)(=O)(O)O>[CH2:14]([N:21]1[CH2:28][C@@H:27]2[CH2:26][N:25]([CH2:29][CH2:30][CH2:31][C:32]3[C:10]4[C:9](=[CH:8][CH:7]=[C:6]([N:4]5[CH:3]=[N:2][N:1]=[CH:5]5)[CH:11]=4)[NH:12][CH:33]=3)[CH2:24][C@@H:23]2[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 51624184-(4-hydrazinylphenyl)-4H-1,2,4-triazoleHCID 21867706HCID 21867706, compound

Product 1

HCID 9888722HCID 9888722, compoundYield 36.3%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

4-(1,2,4-Triazol-4-yl)phenylhydrazine (EP581538) (1.48 g, 8.4 mmol) was added in one portion to a stirred solution of 2-benzyl-5-(5,5-dimethoxypentyl)octahydro-pyrrolo[3,4-c]pyrrole (2.8 g, 8.4 mmol) in 4% sulphuric acid (50 ml) at room temperature. After 30 minutes at room temperature the mixture was heated to reflux under nitrogen for 72h. The reaction was then cooled to 0° C. and quenched with solid potassium carbonate. The aqueous was then extracted with in-butanol (x4). The combined extracts were evaporated and the residue purified by chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (94:5:1→91:8:1→89:10:1) to give the title indole (1.3 g, 35%) as a yellow foam. An analytically pure sample was obtained by further chromatography of a small portion of the above sample on silica gel, eluting with Et2O/EtOH/NH3 (40:10:1) to give the title indole (150 mg) as a colourless solid. The 1.5 hydrogen oxalate. 0.5 hydrate. 0.1 etherate was prepared (Et2O/MeOH): mp 149-153° C. (Found: C, 61.12; H, 6.25; N, 14.07. C26H30N6.1.5(C2H2O4).0.5(H2O). 0.1(C4H10O) requires C, 61.16; H, 6.24; N, 14.26%). δ (360 MHz, d6 -DMSO) 1.98-2.08 (2H, m), 2.50-2.60 (1H, m), 2.70-2.82 (5H, m), 2.86-3.00 (5H, m), 3.06-3.14 (2H, m), 3.38-3.50 (1H, br m), 3.76 (2H, br s, CH2Ph), 7.26-7.38 (7H, m, Ar--H), 7.51 (1H, d, J=8.6 Hz, Ar--H), 7.82 (1H, d, J=2.0 Hz, Ar--H), 9.02 (2H, s, Triazole-H), 11.19 (1H, br s, N--H).

Workup

  1. temperatureto reflux under nitrogen for 72h
  2. temperatureThe reaction was then cooled to 0° C.
  3. customquenched with solid potassium carbonate
  4. extractionThe aqueous was then extracted with in-butanol (x4)
  5. customThe combined extracts were evaporated
  6. customthe residue purified by chromatography on silica gel
  7. washeluting with CH2Cl2 /MeOH/NH3 (94:5:1→91:8:1→89:10:1)

Sources & evidence

ORD record
ord-9238cdd98bd842ed9a8ad9456ca8e730
Source dataset
uspto-grants-2000_08
Patent number
US06107321

Reaction notes

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