Lithium hydroxide, monohydrate → 3-[3-(3-{4-[4-(4'-Chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid

HRID 410368Notes

Reaction equation

HRID 410368 reaction equation
C([O:3][C:4](=[O:52])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([N:31]4[CH2:36][CH2:35][N:34]([CH2:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=5[C:44]5[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=5)[CH2:33][CH2:32]4)=[CH:27][CH:26]=3)[C:16]2=[NH:51])[CH:6]=1)C.O[Li].O>C1COCC1.CO.O>[Cl:50][C:47]1[CH:48]=[CH:49][C:44]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[CH2:37][N:34]2[CH2:35][CH2:36][N:31]([C:28]3[CH:27]=[CH:26][C:25]([CH2:24][N:17]4[C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=5[N:15]([CH2:14][CH2:13][CH2:12][O:11][C:7]5[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=5)[C:4]([OH:52])=[O:3])[C:16]4=[NH:51])=[CH:30][CH:29]=3)[CH2:32][CH2:33]2)=[CH:45][CH:46]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 462412113-[3-(3-{4-[4-(4'-Chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid ethyl ester

Product 1

HCID 462412093-[3-(3-{4-[4-(4'-Chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acidYield 11%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[3-(3-{4-[4-(4′-chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid ethyl ester (140 mg, 0.20 mmol) in THF (1.2 ml), MeOH (1.2 ml) and H2O (0.6 ml) at 0° C. was added LiOH.H2O (16 mg, 0.39 mmol). The reaction was warmed to rt where it was maintained for 20 h. After this time, the mixture was concentrated under reduced pressure and then partitioned between saturated NaHCO3 and dichloromethane to adjust the pH to ˜8. The organic phase was separated, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by preparative HPLC provided 3-[3-(3-{4-[4-(4′-chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid (15 mg, 11%). HPLC-MS 686 [M+1]+, 344.

Workup

  1. temperaturewas maintained for 20 h
  2. concentrationAfter this time, the mixture was concentrated under reduced pressure
  3. custompartitioned between saturated NaHCO3 and dichloromethane
  4. customThe organic phase was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-e21e5e7f4767406598e4065a5b97382a
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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