2'-Hydroxybenzophenone → 2-[(6-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]-4-fluorophenyl]hex-5-ynylimino)phenylmethyl}phenol

HRID 572900

Reaction equation

HRID 572900 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:25][CH:26]1[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]1)[C:11]1[CH:12]=[C:13]([C:18]#[C:19][CH2:20][CH2:21][CH2:22][CH2:23][NH2:24])[CH:14]=[CH:15][C:16]=1[F:17].C([O-])(=O)C([O-])=O.[OH:39][C:40]1[CH:53]=[CH:52][CH:51]=[CH:50][C:41]=1[C:42]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=O>C(O)C.O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:25][CH:26]1[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]1)[C:11]1[CH:12]=[C:13]([C:18]#[C:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]=[C:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:41]2[CH:50]=[CH:51][CH:52]=[CH:53][C:40]=2[OH:39])[CH:14]=[CH:15][C:16]=1[F:17]

Participants

6

Reactant 3

HCID 83482'-HydroxybenzophenoneHCID 71081OxalateHCID 668361616-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]-4-fluorophenyl}hex-5-ynylamine

Product 1

HCID 1363358472-[(6-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]-4-fluorophenyl]hex-5-ynylimino)phenylmethyl}phenol

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 6-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]-4-fluorophenyl}hex-5-ynylamine, oxalate (example 557, 70 mg), 2-hydroxybenzophenone (30 mg) in ethanol (4 mL) is refluxed for 4 h. The mixture is then cooled, diluted with water and extracted with ethyl acetate. Pooled extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/0.5) to afford 2-[(6-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]-4-fluorophenyl}hex-5-ynylimino)phenylmethyl]phenol. TLC (Eluent: CH2Cl2/MeOH/NH4OH 95/5/0.5) Rf=0.15.

Workup

  1. temperatureis refluxed for 4 h
  2. temperatureThe mixture is then cooled
  3. extractionextracted with ethyl acetate
  4. dry with materialPooled extracts are dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/0.5)

Sources & evidence

ORD record
ord-1473753bc426455dbc661dd46d9ccd49
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Linked notes

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