Lithium hydroxide, monohydrate → HCID 57919198, compound

HRID 2381554Notes

Reaction equation

HRID 2381554 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:3]=1[O:4][C:5]1[CH:6]=[N:7][N:8]([CH:12]([CH2:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:13]([NH:15][C:16]2[CH:20]=[C:19]([CH3:21])[N:18]([CH2:22][CH:23]([O:25]C(=O)C)[CH3:24])[N:17]=2)=[O:14])[C:9](=[O:11])[CH:10]=1.O.[OH-].[Li+]>O1CCCC1.O>[F:40][C:36]1[CH:37]=[CH:38][CH:39]=[C:2]([F:1])[C:3]=1[O:4][C:5]1[CH:6]=[N:7][N:8]([CH:12]([CH2:29][CH:30]2[CH2:31][CH2:32][O:33][CH2:34][CH2:35]2)[C:13]([NH:15][C:16]2[CH:20]=[C:19]([CH3:21])[N:18]([CH2:22][CH:23]([OH:25])[CH3:24])[N:17]=2)=[O:14])[C:9](=[O:11])[CH:10]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57919279HCID 57919279, compound

Product 1

HCID 57919198HCID 57919198, compoundYield 70.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of acetic acid 2-{3-[2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-(tetrahydro-pyran-4-yl)-propionylamino]-5-methyl-pyrazol-1-yl}-1-methyl-ethyl ester (Example 131, 170 mg, 0.31 mmol) in tetrahydrofuran (10 mL) and water (2 mL) at 25° C. was treated with lithium hydroxide monohydrate (40 mg, 0.93 mmol). The reaction was stirred at 25° C. for 4.5 h. At this time, the reaction was concentrated in vacuo. Silica gel column chromatography (0 to 60% tetrahydrofuran/hexanes) afforded 2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-propyl)-5-methyl-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide as a white solid (113 mg, 70%); ES+-HRMS m/e calcd for C25H29N5O5F2 [M+H+] 518.2210 found 518.2207. 1H NMR (300 MHz, CDCl3) δ ppm 1.21 (d, J=6.0 Hz, 3H), 1.28-1.51 (m, 3H), 1.54-1.74 (m, 2H), 1.86 (br. s., 1H), 2.14-2.22 (m, 2H), 2.25 (s, 3H), 3.34 (q, J=10.8 Hz, 2H), 3.72-3.84 (m, 1H), 3.88-4.01 (m, 3H), 4.14 (br. s., 1H), 5.64-5.75 (m, 1H), 6.01 (br. s., 1H), 6.49 (s, 1H), 7.09 (t, J=8.5 Hz, 2H), 7.29-7.36 (m, 1H), 8.02 (br. s., 1H), 8.67 (br. s., 1H).

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-7e98550c75f64237bf9daeee49af9b29
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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