Cesium carbonate → (S)-4-((3-Bromopyridin-4-yl)methyl)-7-cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-ylcarbamic acid isopropyl ester

HRID 449837Notes

Reaction equation

HRID 449837 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8]Cl.[CH:10]([O:13][C:14](=[O:30])[NH:15][C@@H:16]1[CH2:29][C:19]2[NH:20][C:21]3[CH:22]=[CH:23][C:24]([C:27]#[N:28])=[CH:25][C:26]=3[C:18]=2[CH2:17]1)([CH3:12])[CH3:11].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C.ClCCl.O>[CH:10]([O:13][C:14](=[O:30])[NH:15][C@@H:16]1[CH2:29][C:19]2[N:20]([CH2:8][C:7]3[CH:6]=[CH:5][N:4]=[CH:3][C:2]=3[Br:1])[C:21]3[CH:22]=[CH:23][C:24]([C:27]#[N:28])=[CH:25][C:26]=3[C:18]=2[CH2:17]1)([CH3:12])[CH3:11]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl EsterHCID 669333093-Bromo-4-(chloromethyl)pyridine

Product 1

HCID 66933638(S)-4-((3-Bromopyridin-4-yl)methyl)-7-cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-ylcarbamic acid isopropyl esterYield 118.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-bromo-4-(chloromethyl)pyridine (3.16 g, 11.5 mmol), ((S)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (2.50 g, 8.82 mmol) and cesium carbonate (4.31 g, 13.2 mmol) in dimethylformamide (20 mL) is stirred at room temperature under nitrogen overnight. The reaction mixture is then diluted with ethyl acetate, dichloromethane, and water. The organic phase is separated, washed with water twice, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to obtain a brown oil (˜4.75 g). The oil is triturated with hexanes twice, then with ether twice. It is then purified by flash chromatography eluting with 30 to 60% ethyl acetate/hexanes to obtain an off-white solid (3.23 g, 81%). LC-ES/MS m/z (79Br/81Br) 453.0/455.0 [M+H]+.

Workup

  1. customThe organic phase is separated
  2. washwashed with water twice
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-912c5da85ab34d98bd5e00be39c125d9
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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