Hydrochloric Acid → 3-{4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid

HRID 1424291Notes

Reaction equation

HRID 1424291 reaction equation
C([O:3][C:4](=[O:35])[CH2:5][CH2:6][NH:7][C:8](=[O:34])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH:28]2[CH2:31][C:30]([CH3:33])([CH3:32])[CH2:29]2)[NH:16][C:17]2[C:26]([CH3:27])=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+].Cl>O1CCCC1.CO>[CH3:32][C:30]1([CH3:33])[CH2:31][CH:28]([CH:15]([NH:16][C:17]2[C:26]([CH3:27])=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)[C:12]2[CH:13]=[CH:14][C:9]([C:8]([NH:7][CH2:6][CH2:5][C:4]([OH:35])=[O:3])=[O:34])=[CH:10][CH:11]=2)[CH2:29]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 71239546(+/-)-3-{4-[(3,3-Di methyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester2×

Product 1

HCID 712395123-{4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acidYield 120.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(+/−)-3-{4-[(3,3-di methyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester (Intermediate 27) (36 mg, 0.076 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (1 mL), and 1.0 M sodium hydroxide (2 mL) was added. This was stirred as a solution at room temperature for 45 min before 1 N HCl was added to bring to pH 4.5. This was extracted twice with ethyl acetate and the combined organics dried over MgSO4. The solution was concentrated in vacuo to give (+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid (40.8 mg) as a white solid impure with ethyl acetate. MS (M+1): 446.3. HPLC: XBridge C18 150 mm×4.6 mm, 5 μm column, flow rate 1.50 mL/min, linear gradient of 5% acetonitrile/water (0.1% trifluoroacetic acid modifier) to 100% acetonitrile over 11 min, Retention time=7.046 min.

Workup

  1. additionwas added
  2. extractionThis was extracted twice with ethyl acetate
  3. dry with materialthe combined organics dried over MgSO4
  4. concentrationThe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-1e826ebd35714f50b9c29121b224497c
Source dataset
uspto-grants-2015_01
Patent number
US08927577B2

Reaction notes

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