Triethylamine → 1-(4-chloro-phenyl)-4-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-piperazine-2-carbonitrile

HRID 457176Notes

Reaction equation

HRID 457176 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][NH:11][CH2:12][CH2:13][CH:14]=[C:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[N:25][C:20]=3[CH2:19][O:18][C:17]3[CH:26]=[CH:27][C:28]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:29][C:16]2=3)=[CH:4][CH:3]=1.[CH2:34]([N:36](CC)CC)C.Br[CH:42](CBr)[C:43]#N>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:43][CH2:42][N:11]([CH2:12][CH2:13][CH:14]=[C:15]3[C:21]4[CH:22]=[CH:23][CH:24]=[N:25][C:20]=4[CH2:19][O:18][C:17]4[CH:26]=[CH:27][C:28]([C:30]([OH:33])([CH3:31])[CH3:32])=[CH:29][C:16]3=4)[CH2:10][CH:9]2[C:34]#[N:36])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1072992,3-DibromopropanenitrileHCID 667582672-(5-{3-[2-(4-Chloro-phenylamino)-ethylamino]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl)-propan-2-ol

Product 1

HCID 667585841-(4-chloro-phenyl)-4-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-piperazine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-(5-{3-[2-(4-chloro-phenylamino)-ethylamino]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl)-propan-2-ol (0.4 g, 0.87 mmol) in toluene (6 mL) was added triethylamine (0.48 mL, 3.44 mmol) and 2,3-dibromopropionitrile (0.19 mL, 1.72 mmol) and reaction mixture was heated to 110° C. (reflux) and stirred overnight for 18 h. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate and extracted with 1.0N NaOH solution. The aqueous layer was back extracted twice with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated. The crude product was purified using a short plug of silica gel using ethyl acetate to give the desired product. 1H-NMR (CDCl3) δ: 1.05 (6H, s), 2.20–2.70 (8H, 2×m), 3.00 (1H, m), 3.10–3.40 (3H, 2×m), 4.50 (1H, br, s), 5.30 (2H, br, s), 6.20 (1H, t), 6.70–6.90 (3H, 2×d), 7.10–7.35 (4H, m), 7.50 (2H, d), 8.50 (1H, dd). ESI-MS m/z: 515 (M+1), UV retention time: 2.36 min.

Workup

  1. temperature(reflux)
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additionthe residue was diluted with ethyl acetate
  4. extractionextracted with 1.0N NaOH solution
  5. extractionThe aqueous layer was back extracted twice with ethyl acetate
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-88c6bf8afc1e49d9bb1caf48653e0408
Source dataset
uspto-grants-2007_03
Patent number
US07186729B2

Reaction notes

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