Lithium Hydroxide → (+/-)-N-[4-(1-{[6-(4-cyclopropyl-1H-pyrazol-1-yl)pyridin-3-yl]amino}butyl)benzoyl]-beta-alanine

HRID 1520965Notes

Reaction equation

HRID 1520965 reaction equation
[CH:1]1([C:4]2[CH:5]=[N:6][N:7]([C:9]3[N:14]=[CH:13][C:12]([NH:15][CH:16]([C:20]4[CH:35]=[CH:34][C:23]([C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])=[O:25])=[CH:22][CH:21]=4)[CH2:17][CH2:18][CH3:19])=[CH:11][CH:10]=3)[CH:8]=2)[CH2:3][CH2:2]1.O1CCCC1.[OH-].[Li+].FC(F)(F)C(O)=O>CO.O.C(#N)C>[CH:1]1([C:4]2[CH:5]=[N:6][N:7]([C:9]3[N:14]=[CH:13][C:12]([NH:15][CH:16]([C:20]4[CH:21]=[CH:22][C:23]([C:24]([NH:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:25])=[CH:34][CH:35]=4)[CH2:17][CH2:18][CH3:19])=[CH:11][CH:10]=3)[CH:8]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 86669098(+/-)-ethyl N-[4-(1-[{6-(4-cyclopropyl-1H-pyrazol-1-yl)pyridin-3-yl]amino}butyl)benzoyl]-beta-alaninate

Product 1

HCID 68156526(+/-)-N-[4-(1-{[6-(4-cyclopropyl-1H-pyrazol-1-yl)pyridin-3-yl]amino}butyl)benzoyl]-beta-alanine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 18373917Acetonitrile--water (1/1)Solvent3×

Procedure

A mixture of crude (+/−)-ethyl N-[4-(1-{[6-(4-cyclopropyl-1H-pyrazol-1-yl)pyridin-3-yl]amino}butyl)benzoyl]-beta-alaninate (63 mg, 0.13 mmol) was dissolved in methanol (0.26 ml) and tetrahydrofuran (0.13 ml) and treated with aqueous 2.0M lithium hydroxide (0.13 ml, 0.26 mmol). The mixture was stirred at ambient temperature for 12 hours. The reaction was concentrated in vacuo. The residue was acidified with aqueous 1.0M hydrochloric acid and concentrated in vacuo a second time. Purification by reversed-phase HPLC on a Waters Sunfire C18 19×100 mm, 0.005 mm column eluting with a gradient of water in acetonitrile (0.05% trifluoroacetic acid modifier) gave the product. Analytical LCMS: retention time 2.94 minutes (Atlantis C18 4.6×50 mm, 5 μM column; 95% water/acetonitrile linear gradient to 5% water/acetonitrile over 4.0 minutes, hold at 5% water/acetonitrile to 5.0 minutes; 0.05% trifluoroacetic acid modifier; flow rate 2.0 mL/minute); MS (M+1): 448.2.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. concentrationconcentrated in vacuo a second time
  3. customPurification by reversed-phase HPLC on a Waters Sunfire C18 19×100 mm, 0.005 mm column
  4. washeluting with a gradient of water in acetonitrile (0.05% trifluoroacetic acid modifier)
  5. customgave the product

Sources & evidence

ORD record
ord-dbc92fe9731c465ab2a119159cde231e
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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