Ethyl isocyanate → HCID 67219000, compound

HRID 1788287Notes

Reaction equation

HRID 1788287 reaction equation
[Cl:1][C:2]1[C:40]([Cl:41])=[CH:39][C:5]2[NH:6][C:7]([O:9][CH:10]([C:19]3([C:25]4[CH:30]=[CH:29][C:28]([C:31]5[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=5)=[CH:27][CH:26]=4)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[N:8][C:4]=2[CH:3]=1.[CH2:42]([N:44]=[C:45]=[O:46])[CH3:43].C(N(C(C)C)CC)(C)C>ClCCl>[CH2:42]([NH:44][C:45]([N:22]1[CH2:23][CH2:24][C:19]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=3)=[CH:27][CH:26]=2)([CH:10]([O:9][C:7]2[NH:8][C:4]3[CH:3]=[C:2]([Cl:1])[C:40]([Cl:41])=[CH:39][C:5]=3[N:6]=2)[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH2:20][CH2:21]1)=[O:46])[CH3:43]

Participants

5

Reactant 3

HCID 8022Ethyl isocyanateHCID 81531DiisopropylethylamineHCID 67218842HCID 67218842, compound

Product 1

HCID 67219000HCID 67219000, compoundYield 60.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.045 g of 4′-{4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidin-4-yl}-biphenyl-3-carbonitrile (0.073 mmol, 1 eq) in 0.7 mL of dichloromethane was added ethyl isocyanate (6.5 μL, 0.088 mmol, 1.2 eq) and 15.4 μL of diisopropylethyl amine (0.088 mmol, 1.2 eq) and the resulting mixture was stirred at room temperature for 16 h. The solvent was removed by rotary evaporation to yield the crude product which was purified by preparative TLC eluting with 10% methanol in dichloromwthane to give 0.030 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidine-1-carboxylic acid ethylamide. This intermediate was dissolved in 2 mL of tetrahydrofuran and 0.080 g of tetrabutylammonium fluoride on silica gel (1.0-1.5 mmol/g, 2 eq) was added. The mixture was heated at 60° C. for 16 h then filtered and the resin washed with 10 mL of tetrahydrofuran. The filtrate was concentrated by rotary evaporation and the crude product was purified by flash silica gel chromatography eluting with 1% methanol in dichloromethane with 3% triethylamine to give 0.0054 g of the desired product 4-(3′-cyano-biphenyl-4-yl)-4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidine-1-carboxylic acid ethylamide 58. MS (ESI): Calcd m/z for C29H27Cl2N5O2.H+=548.2; found m/z=547.8/549.8 [(M+1)+/(M+3)+].

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customto yield the crude product which
  3. customwas purified by preparative TLC
  4. washeluting with 10% methanol in dichloromwthane

Sources & evidence

ORD record
ord-63d2c51d78ef4c92b9fdbf9eed4b7d71
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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