Hydrochloric Acid → HCID 57970139, compound

HRID 1666645Notes

Reaction equation

HRID 1666645 reaction equation
[C:1]1([CH2:13][C:14]([N:16]2[CH2:20][CH2:19][C@H:18]([NH:21][C:22]3[N:31]=[C:30]([N:32]4[CH2:37][CH2:36][CH:35]([C:38]([O:40]CC)=[O:39])[CH2:34][CH2:33]4)[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=3)[CH2:17]2)=[O:15])(C2C=CC=CC=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH2:2]1.[OH-].[Na+].Cl>CO>[C:2]1([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH2:13][C:14]([N:16]1[CH2:20][CH2:19][C@H:18]([NH:21][C:22]2[N:31]=[C:30]([N:32]3[CH2:37][CH2:36][CH:35]([C:38]([OH:40])=[O:39])[CH2:34][CH2:33]3)[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)[CH2:17]1)=[O:15]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67441728HCID 67441728, compound

Product 1

HCID 57970139HCID 57970139, compoundYield 107.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ethyl 1-(2-((S)-1-(2-biphenyl-1-ylethanoyl)pyrrolidin-3-ylamino)quinazolin-4-yl)piperidine-4-carboxylate (0.59 g) synthesized in the same manner as the method described in Example 1 was dissolved in methanol (4.5 mL), followed by addition of 2.2 M aqueous sodium hydroxide (1.3 mL), and the mixture was stirred at room temperature for 1 day. 1 M hydrochloric acid was added until the reaction solution became pH 7, the mixture was stirred at room temperature for 2 days, and then the precipitated solids were collected by filtration to obtain 1-(2-((S)-1-(2-biphenyl-2-ylethanoyl)pyrrolidin-3-ylamino)quinazolin-4-yl)piperidine-4-carboxylic acid (0.30 g). (2) To a mixture of 1-(2-((S)-1-(2-biphenyl-2-ylethanoyl)pyrrolidin-3-ylamino)quinazolin-4-yl)piperidine-4-carboxylic acid (0.17 g) and DMF (5.0 mL) were added EDC.HCl (85 mg) and HOBt.H2O (77 mg), followed by addition of 28% aqueous NH3 (0.023 mL), and the mixture was stirred at room temperature for 17 h. The reaction solution was diluted with ethyl acetate and then washed with saturated aqueous sodium hydrogencarbonate, water, and saturated brine, and the organic layer was dried with anhydrous sodium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, then the residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol=10:1), and then the resulting compound was crystallized in diethyl ether to obtain 1-(2-((S)-1-(2-biphenyl-2-ylethanoyl)pyrrolidin-3-ylamino)quinazolin-4-yl)piperidine-4-carboxylic acid amide (160 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 2 days
  2. filtrationthe precipitated solids were collected by filtration

Sources & evidence

ORD record
ord-b9c5a41c1c1f4d7c9a490a428e6af6a1
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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