Ammonia → HCID 57970084, compound

HRID 1666646Notes

Reaction equation

HRID 1666646 reaction equation
NN1[CH2:6][CH2:5][CH2:4][CH2:3]1.[C:7]1(C2C=CC=CC=2)[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=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)[CH2:34][CH2:33]3)C3C(=CC=CC=3)N=2)[CH2:17]1)=[O:15].[CH3:47][CH2:48]N=C=NCCCN(C)C.Cl.[CH:59]1[CH:60]=[CH:61][C:62]2N(O)N=[N:65][C:63]=2[CH:64]=1.[NH3:69]>C(OCC)(=O)C.O.CN(C=O)C>[C:7]1([C:3]2[CH:48]=[CH:47][CH:6]=[CH:5][CH:4]=2)[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=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]([NH2:69])=[O:40])[CH2:34][CH2:33]3)[C:62]3[C:63](=[CH:64][CH:59]=[CH:60][CH:61]=3)[N:65]=2)[CH2:17]1)=[O:15]

Participants

9

Reactant 5

HCID 222AmmoniaHCID 279461-PyrrolidinamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57970139HCID 57970139, compound

Product 1

HCID 57970084HCID 57970084, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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. washwashed with saturated aqueous sodium hydrogencarbonate, water, and saturated brine
  2. dry with materialthe organic layer was dried with anhydrous sodium sulfate
  3. customThe desiccant was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol=10:1)
  6. customthe resulting compound was crystallized in diethyl ether

Sources & evidence

ORD record
ord-62b2143e807e42f581a41c1b471b7e5a
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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