Potassium Iodide → [(4-Chloro-benzyl)-(1-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-pyrrolidin-3-yl)-amino]-acetic Acid Methyl Ester

HRID 1983741Notes

Reaction equation

HRID 1983741 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][N:5]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[CH:6]1[CH2:10][CH2:9][NH:8][CH2:7]1.N1C(C)=CC=CC=1C.[I-].[K+].Br[CH2:31][CH2:32][CH:33]=[C:34]1[C:40]2[CH:41]=[CH:42][CH:43]=[N:44][C:39]=2[CH2:38][O:37][C:36]2[CH:45]=[CH:46][C:47]([C:49]([OH:52])([CH3:51])[CH3:50])=[CH:48][C:35]1=2>C(O)(C)C>[CH3:1][O:2][C:3](=[O:19])[CH2:4][N:5]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)[CH:6]1[CH2:10][CH2:9][N:8]([CH2:31][CH2:32][CH:33]=[C:34]2[C:40]3[CH:41]=[CH:42][CH:43]=[N:44][C:39]=3[CH2:38][O:37][C:36]3[CH:45]=[CH:46][C:47]([C:49]([OH:52])([CH3:51])[CH3:50])=[CH:48][C:35]2=3)[CH2:7]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 79372,6-LutidineHCID 666859992-[5-(3-Bromo-propylidene)-5,1 1-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-propan-2-olHCID 66758681[(4-Chloro-benzyl)-pyrrolidin-3-yl-amino]-acetic acid methyl ester

Product 1

HCID 66758164[(4-Chloro-benzyl)-(1-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-pyrrolidin-3-yl)-amino]-acetic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of [(4-Chloro-benzyl)-pyrrolidin-3-yl-amino]-acetic acid methyl ester (188 mg, 0.67 mmol) in isopropanol (5 mL) was added 2,6-lutidine (186 uL, 1.6 mmol), and a catalytic amount of potassium iodide. The resultant solution was heated at 80° C. and to it was added 2-[5-(3-Bromo-propylidene)-5,1 1-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-propan-2-ol (149 mg, 0.4 mmol) portionwise over 0.5 h. The reaction solution was heated overnight then partitioned between water and ethyl acetate. The product was purified on SiO2 (ethyl acetate:methanol:triethylamine 95:4.5:0.4) and isolated as a film. LCMS (retention time=1.84, ES+; 576); 1H NMR (CD3OD): δ 8.46 (1H, d), 7.76 (1H, d), 7.45 (2H, m), 7.23 (5H, m), 6.74 (1H, d), 6.15 (1H, m), 3.72 (2H, m), 3.60 (4H, s), 3.30 (6H, m), 2.78 (4H, m), 2.42 (2H, m), 2.05 (1H, m), 1.82 (1H, m), 1.50 (6H, s)

Workup

  1. temperatureThe reaction solution was heated overnight
  2. customthen partitioned between water and ethyl acetate
  3. customThe product was purified on SiO2 (ethyl acetate:methanol:triethylamine 95:4.5:0.4)
  4. customisolated as a film

Sources & evidence

ORD record
ord-ed3591165f63436ca83c1a8ba26916b7
Source dataset
uspto-grants-2009_06
Patent number
US07541365B2

Reaction notes

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