Water → HCID 178480512, compound

HRID 2404470Notes

Reaction equation

HRID 2404470 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-7962d48d3cda48539e489b7ea1ca216a
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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