5-Fluoro-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)-benzoylamino]benzoic acid → 6-Fluoro-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)phenyl]-4H-3,1-benzoxazin-4-one

HRID 644229Notes

Reaction equation

HRID 644229 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12](=O)[C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:15][C:14]=2[O:24][CH:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]>CN(C=O)C.[Cl-].[Na+].O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:12]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:15][C:14]=3[O:24][CH:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[O:9][C:7](=[O:8])[C:6]=2[CH:10]=1

Participants

4

Reactant 1

HCID 685305135-Fluoro-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)-benzoylamino]benzoic acid

Product 1

HCID 578608426-Fluoro-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)phenyl]-4H-3,1-benzoxazin-4-oneYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 5-fluoro-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)-benzoylamino]benzoic acid (7.4 g, 16.8 mmol) in dry DMF (120 mL) was treated with S1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.42 g, 33.5 mmol). The reaction was stirred at ambient temperature overnight. The mixture was poured into brine (300 mL) and extracted with 10% MeOH in EtOAc (3×100 mL). The combined extracts were washed with water (2×400 mL), then brine (2×400 mL), dried over MgSO4, and concentrated to a solid which was purified by chromatography on silica, using 40/55/5 THF/Hex/Et3 N in hexanes, to give 3.4 g (48%) of a yellow solid.

Workup

  1. extractionextracted with 10% MeOH in EtOAc (3×100 mL)
  2. washThe combined extracts were washed with water (2×400 mL)
  3. dry with materialbrine (2×400 mL), dried over MgSO4
  4. concentrationconcentrated to a solid which
  5. customwas purified by chromatography on silica

Sources & evidence

ORD record
ord-fa8c0efeaaeb418ea42575948adf0697
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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