Lithium Hydroxide → 2-[6-[(4-Tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5h-pyrido[2,3-b][1,5]benzodiazepin-8-yl]-2-methylpropanoic acid

HRID 1691446Notes

Reaction equation

HRID 1691446 reaction equation
C[O:2][C:3](=[O:39])[C:4]([C:7]1[CH:8]=[CH:9][C:10]2[NH:16][C:15]3[N:17]=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:19]=[CH:20][C:14]=3[CH2:13][N:12]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:11]=2[CH:38]=1)([CH3:6])[CH3:5].[Li+].[OH-]>O.C1COCC1.C(#N)C>[C:34]([C:31]1[CH:30]=[CH:29][C:28]([S:25]([N:12]2[C:11]3[CH:38]=[C:7]([C:4]([CH3:6])([CH3:5])[C:3]([OH:39])=[O:2])[CH:8]=[CH:9][C:10]=3[NH:16][C:15]3[N:17]=[C:18]([C:21]([F:23])([F:22])[F:24])[CH:19]=[CH:20][C:14]=3[CH2:13]2)(=[O:26])=[O:27])=[CH:33][CH:32]=1)([CH3:35])([CH3:36])[CH3:37]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 596187022-[6-[(4-tert-Butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]-2-methylpropanoic acid methyl ester

Product 1

HCID 596186742-[6-[(4-Tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5h-pyrido[2,3-b][1,5]benzodiazepin-8-yl]-2-methylpropanoic acid

Reagents, catalysts & solvents 1

HCID 18694733Acetonitrile tetrahydrofuran waterSolvent

Procedure

To the methyl ester (92 mg, 0.16 mmol) of Example 373 in 3 mL of H2O/THF/acetonitrile (1:1:1) was added LiOH (16 mg, 0.65 mmol). After stirring at rt for 48 hrs, the reaction was quenched with aqueous NH4Cl (25 mL) and the product was extracted with EtOAc (60 mL). The extracts were washed with water (30 mL) and brine (30 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified on silica gel column eluting with 20-50% EtOAc in hexanes to afford the title compound. 1H NMR (500 MHz, CD3OD): δ 7.61 (1H, d), 7.46 (1H, s), 7.24 (1H, d), 7.17 (2H, d), 7.03 (1H, d), 6.93 (1H, d), 6.91 (2H, d), 1.58 (6H, s), 1.22 (9H, s). LCMS: m/e 548.2 (M+H)+.

Workup

  1. customthe reaction was quenched with aqueous NH4Cl (25 mL)
  2. extractionthe product was extracted with EtOAc (60 mL)
  3. washThe extracts were washed with water (30 mL) and brine (30 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on silica gel column
  8. washeluting with 20-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-224f0abf0f4e4f32aad66088522e6a02
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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