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 557044Notes

Reaction equation

HRID 557044 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][NH:25][C:20]3=[CH: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 669925862-(5-{3-[2-(4-Chloro-phenylamino)-ethylamino]-propylidene}-5,1-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}-5,1-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-47d48abeb7a84f278f2dfce0b19e538a
Source dataset
uspto-grants-2011_11
Patent number
US08058287B2

Reaction notes

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