Trifluoroacetic acid → HCID 11363568, compound

HRID 1788283Notes

Reaction equation

HRID 1788283 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]#[N:40])[CH:34]=3)=[CH:29][CH:28]=2)([CH2:14][O:15][C:16]2[NH:20][C:19]3[CH:21]=[C:22]([Cl:26])[C:23]([Cl:25])=[CH:24][C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl.C1(C)C=CC=CC=1>[Cl:26][C:22]1[C:23]([Cl:25])=[CH:24][C:18]2[NH:17][C:16]([O:15][CH2:14][C:11]3([C:27]4[CH:28]=[CH:29][C:30]([C:33]5[CH:38]=[CH:37][CH:36]=[C:35]([C:39]#[N:40])[CH:34]=5)=[CH:31][CH:32]=4)[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[N:20][C:19]=2[CH:21]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11157447HCID 11157447, compound

Product 1

HCID 11363568HCID 11363568, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 0.015 g of 4-(3′-cyano-biphenyl-4-yl)-4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester 53 (0.026 mmol) in 3 mL of dichloromethane at 0° C. was added 1 mL of trifluoroacetic acid. The mixture was stirred at 0° C. for 2 h then diluted with 10 mL of toluene and concentrated by rotary evaporation. The resulting residue was dissolved in 25 m) of ethyl acetate and washed with 10% aqueous NaHCO3 and saturated brine. The organic extracts were dried over Na2SO4, filtered and concentrated by rotary evaporation to give the crude product which was purified by reverse phase preparative HPLC to give 0.0113 g of the desired product 4′-[4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidin-4-yl]-biphenyl-3-carbonitrile 54 as a pale foam. 1H NMR (300 MHz, CDCl3/CD3OD): δ 7.85-7.75 (t, 1H), 7.72-7.70 (dt, 1H), 7.57-7.41 (m, 6H), 7.30(s, 2H), 5.19 (s, 2H), 4.31 (s, 2H), 3.33-3.25 (m, 2H), 2.90-2.82 (d, 2H), 2.47-2.34 (m, 2H), MS (ESI): Calcd m/z for C26H22Cl2N4O.H+=477.1. Found m/z=476.7/478.7 [(M+1)+/(M+3)+].

Workup

  1. concentrationconcentrated by rotary evaporation
  2. dissolutionThe resulting residue was dissolved in 25 m) of ethyl acetate
  3. washwashed with 10% aqueous NaHCO3 and saturated brine
  4. dry with materialThe organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customto give the crude product which
  8. customwas purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-833505e716b6420083758a04c4baeb6d
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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