Water → HCID 178480512, compound

HRID 572879Notes

Reaction equation

HRID 572879 reaction equation
[F:1][C:2]1[CH:41]=[CH:40][C:5]2[NH:6][C:7]([CH:9]([O:32][CH:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)[C:10]3[CH:11]=[C:12]([C:16]#[C:17][CH2:18][CH2:19][CH2:20][N:21]4C(=O)C5C(=CC=CC=5)C4=O)[CH:13]=[CH:14][CH:15]=3)=[N:8][C:4]=2[CH:3]=1.O.NN.O.[C:46]([OH:51])(=[O:50])[C:47]([OH:49])=[O:48]>C(O)C.CC(C)=O>[C:46]([OH:51])(=[O:50])[C:47]([OH:49])=[O:48].[F:1][C:2]1[CH:41]=[CH:40][C:5]2[NH:6][C:7]([CH:9]([O:32][CH:33]3[CH2:34][CH2:35][N:36]([CH3:39])[CH2:37][CH2:38]3)[C:10]3[CH:11]=[C:12]([C:16]#[C:17][CH2:18][CH2:19][CH2:20][NH2:21])[CH:13]=[CH:14][CH:15]=3)=[N:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 971Oxalic AcidHCID 24654Hydrazine hydrate (1:1)HCID 178480511HCID 178480511, compound

Product 1

HCID 178480512HCID 178480512, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 702EthanolSolvent

Procedure

A solution of 2-(5-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenyl}pent-4-ynyl)isoindole-1,3-dione (example 438B, 170 mg) and hydrazine hydrate (200 μL) in ethanol (2.5 mL) is stirred a room temperature overnight. Water is added and the aqueous phase is extracted by diethyl ether. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (dichloromethane/methanol/ammonia from 95/5/0.5 to 90/10/1)) to afford the free base. One equivalent of oxalic acid in acetone is added to the free base to afford 5-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenyl}pent-4-ynylamine oxalate as a white crystalline solid melting at 150° C.

Workup

  1. extractionthe aqueous phase is extracted by diethyl ether
  2. dry with materialThe pooled organic extracts are dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by chromatography (dichloromethane/methanol/ammonia from 95/5/0.5 to 90/10/1))
  5. customto afford the free base

Sources & evidence

ORD record
ord-f318879b34ab48f2922428720594077d
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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