Tetrahydrofuran → (3S,4R)-3-((tert-butoxycarbonyl)amino)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclopentane-1-carboxylic acid

HRID 56391Notes

Reaction equation

HRID 56391 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:13]([NH:14][C:15]2[N:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:25]4[C:30]([Cl:31])=[C:29]([O:32][CH3:33])[CH:28]=[C:27]([O:34][CH3:35])[C:26]=4[Cl:36])[CH:21]=3)[N:16]=2)[CH2:12][CH:11]([C:37]([O:39]C)=[O:38])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Na+]>CO>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:13]([NH:14][C:15]2[N:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:25]4[C:26]([Cl:36])=[C:27]([O:34][CH3:35])[CH:28]=[C:29]([O:32][CH3:33])[C:30]=4[Cl:31])[CH:21]=3)[N:16]=2)[CH2:12][CH:11]([C:37]([OH:39])=[O:38])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 118036222Methyl (3S,4R)-3-((tert-butoxycarbonyl)amino)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)-quinazolin-2-yl)amino)cyclopentane-1-carboxylate

Product 1

HCID 118036129(3S,4R)-3-((tert-butoxycarbonyl)amino)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclopentane-1-carboxylic acidYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl (3S,4R)-3-((tert-butoxycarbonyl)amino)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)-quinazolin-2-yl)amino)cyclopentane-1-carboxylate (0.662 g, 1.119 mmol) was taken up in methanol (10 ml), THF (4 ml) and treated with 10 ml of 1N NaOH. The reaction mixture was stirred at room temperature for 2 hours. The organic solvents were removed under reduced pressure, then the aqueous layer was acidified with 1N HCl to pH ˜2. The aqueous layer was extracted with EtOAcx3. The organic layers were combined, dried over sodium sulfate, and the solvent removed to give crude (3S,4R)-3-((tert-butoxycarbonyl)amino)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclopentane-1-carboxylic acid (0.580 g, 1.00 mmol, 91% yield) which was carried on with further purification. MS (ES+) C27H30Cl2N4O6 requires: 577, found: 578 [M+H]+.

Workup

  1. customThe organic solvents were removed under reduced pressure
  2. extractionThe aqueous layer was extracted with EtOAcx3
  3. dry with materialdried over sodium sulfate
  4. customthe solvent removed

Sources & evidence

ORD record
ord-58ba660d6d7445e2b0dae34dcc86da6b
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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