Sodium Hydroxide → HCID 58318667, compound

HRID 1027933Notes

Reaction equation

HRID 1027933 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[C:5]([F:35])=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:33][CH3:34])=[C:18]([O:21][C@@H:22]4[CH2:27][CH2:26][N:25]([CH3:28])[C@H:24]([C:29]([O:31]C)=[O:30])[CH2:23]4)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1>C1COCC1.CO>[Cl:3][C:4]1[C:5]([F:35])=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:33][CH3:34])=[C:18]([O:21][C@@H:22]4[CH2:27][CH2:26][N:25]([CH3:28])[C@H:24]([C:29]([OH:31])=[O:30])[CH2:23]4)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 58318671HCID 58318671, compound

Product 1

HCID 58318667HCID 58318667, compoundYield 59.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2N NaOH (1.3 ml, 2.66 mmol) was added to a solution of methyl (2S,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-1-methylpiperidine-2-carboxylate (14) (0.252 g, 0.53 mmol) in THF (5 ml) and methanol (1 ml). The reaction mixture was stirred overnight at room temperature and evaporated to dryness. The residues were dissolved in water (10 ml) and the solution acidified to pH6 with 2N HCl. The resulting solids were collected by filtration, washed with water (5 ml) followed by diethylether (5 ml) and dried under vacuum to give (2S,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-1-methylpiperidine-2-carboxylic acid (15) as a cream solid (145 mg, 59%): 1H NMR Spectrum: (DMSO-d6) δ1.72-1.90 (2H, m), 2.20-2.31 (1H, m), 2.40-2.55 (1H+DMSO, m), 2.66 (3H, s), 2.84-2.94 (1H, m), 3.10-4.10 (2H, m), 3.95 (3H, s), 4.56-4.60 (1H, m), 7.18-7.25 (2H, m), 7.48-7.55 (2H, m), 8.05 (1H, s), 8.40 (1H, s); Mass Spectrum: (M+H)+ 461.

Workup

  1. customevaporated to dryness
  2. dissolutionThe residues were dissolved in water (10 ml)
  3. filtrationThe resulting solids were collected by filtration
  4. washwashed with water (5 ml)
  5. customdried under vacuum

Sources & evidence

ORD record
ord-522ffba0ae104040a6cbe5be1ca11f38
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

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