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 410368ノート

反応式

HRID 410368 の反応式
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

参加物

6

反応物 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

生成物 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 acid収率 11%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e21e5e7f4767406598e4065a5b97382a
出典データセット
uspto-grants-2014_06
特許番号
US08759520B2

反応ノート

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