Lithium Hydroxide → HCID 57920040, compound

HRID 19169Notes

Reaction equation

HRID 19169 reaction equation
C([O:3][C:4](=[O:36])[CH2:5][N:6]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:35])[C@@H:13]([N:18]2[CH2:22][C:21]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]4[CH2:32][CH2:31]4)[C:25]=3[F:33])=[CH:20][C:19]2=[O:34])[CH2:14][CH:15]([CH3:17])[CH3:16])=[N:7]1)C.[OH-].[Li+]>O1CCCC1>[CH:30]1([C:26]2[C:25]([F:33])=[C:24]([CH:29]=[CH:28][CH:27]=2)[O:23][C:21]2[CH2:22][N:18]([C@@H:13]([CH2:14][CH:15]([CH3:16])[CH3:17])[C:12]([NH:11][C:8]3[CH:9]=[CH:10][N:6]([CH2:5][C:4]([OH:36])=[O:3])[N:7]=3)=[O:35])[C:19](=[O:34])[CH:20]=2)[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 57920089(3-{(S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-yl)-acetic acid ethyl ester

Product 1

HCID 57920040HCID 57920040, compoundYield 96.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-{(S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-yl)-acetic acid ethyl ester (prepared as in Example 148, 0.130 g, 0.26 mmol) in tetrahydrofuran (5 mL) was added an aqueous lithium hydroxide solution (0.5N, 2 mL). The resulting mixture was stirred at room temperature for 3 h. The solvents were evaporated and the residue neutralized with 1N aqueous hydrochloric acid, extracted with ethyl acetate. The combined organic layers were washed with water, saturated sodium chloride solution and dried over sodium sulfate. The mixture was filtered and evaporated which afforded (3-{(S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-yl)-acetic acid (0.118 g, 96%) as a white solid: HR-ES-MS m/z calculated for C24H27FN4O5 [M+H]+ 471.2038 observed 471.2036; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.72-0.81 (m, 2H), 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 0.97-1.06 (m, 2H), 1.37-1.51 (m, 1H), 1.52-1.65 (m, 1H), 1.65-1.82 (m, 1H), 2.00-2.15 (m, 1H), 4.21 (d, J=18.4 Hz, 1H), 4.59 (d, J=18.4 Hz, 1H), 4.62 (s, 2H), 4.86 (s, 1H), 4.85-4.93 (m, 1H), 6.42 (d, J=2.0 Hz, 1H), 6.94 (t, J=6.9 Hz, 1H), 7.15 (t, J=7.8 Hz, 1H), 7.21-7.31 (m, 1H), 7.54 (d, J=2.0 Hz, 1H), 10.75 (s, 1H).

Workup

  1. customThe solvents were evaporated
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with water, saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationThe mixture was filtered
  6. customevaporated which

Sources & evidence

ORD record
ord-54935154868941a980689988b23bd213
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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