Lithium hydroxide, monohydrate → HCID 66899437, compound

HRID 19385Notes

Reaction equation

HRID 19385 reaction equation
C[O:2][C:3](=[O:26])[C@@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH:17]=[N:18][N:19]3[CH3:24])=[CH:11][C:10]1=[O:25])[CH2:5][CH:6]([CH3:8])[CH3:7].O.[OH-].[Li+]>O1CCCC1.O>[CH3:7][CH:6]([CH3:8])[CH2:5][C@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH:17]=[N:18][N:19]3[CH3:24])=[CH:11][C:10]1=[O:25])[C:3]([OH:26])=[O:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66899863HCID 66899863, compound

Product 1

HCID 66899437HCID 66899437, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-4-methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester (30 mg, 0.08 mmol) in tetrahydrofuran (5 mL) and water (1 mL) was treated with lithium hydroxide monohydrate (3.6 mg 0.08 mmol). The mixture was stirred at room temperature for 3.5 h and then partitioned between ethyl acetate and water. The aqueous phase was acidified with 1N aqueous hydrochloric acid (pH=1), and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford (S)-4-methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid as an off-white solid. A mixture of (S)-4-methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid in dichloromethane (5 mL) was treated with 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.025 g, 0.13 mmol), N,N-diisopropylethylamine (0.033 g, 0.26 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.056 g, 0.13 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 3.5 h. The mixture was partioned between dichloromethane and water. The organic layer was collected and concentrated in vacuo and the residue was purified by flash column chromatography (silica gel, 20% to 100% ethyl acetate/hexanes) which afforded (S)-4-Methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (0.025 g, 57%) as an off-white solid.

Workup

  1. custompartitioned between ethyl acetate and water
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-51c17e4bfe6743aeb253ab9ea3ad0a42
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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