2-Fluoroaniline → 5-Fluoro-N-(2-fluorophenyl)-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]benzamide

HRID 644230Notes

Reaction equation

HRID 644230 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].C([Mg]Br)C=C.[F:14][C:15]1[CH:16]=[CH:17][C:18]2[N:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:26][C:25]=3[O:35][CH:36]3[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]3)[O:21][C:20](=[O:43])[C:19]=2[CH:44]=1.[N-]=C=O>C1COCC1.C(OCC)C>[F:14][C:15]1[CH:16]=[CH:17][C:18]([NH:23][C:22](=[O:21])[C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:31][CH2:32][CH2:33][CH2:34]3)=[CH:26][C:25]=2[O:35][CH:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[C:19]([CH:44]=1)[C:20]([NH:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[F:1])=[O:43]

Participants

7

Reactant 4

HCID 95842-FluoroanilineHCID 105034IsocyanateHCID 578608426-Fluoro-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)phenyl]-4H-3,1-benzoxazin-4-oneHCID 178455850HCID 178455850, compound

Product 1

HCID 578608755-Fluoro-N-(2-fluorophenyl)-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]benzamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-fluoroaniline (22.1 mg, 0.18 mmol) in dry THF (1 mL) was treated with a 1 M diethyl ether solution of allyl magnesium bromide (0.2 mL). The reaction was stirred for 5 minutes before adding 6-fluoro-2-[4-(pyrrolidin-1-yl)-2-(1-methylpiperidin-4-yloxy)phenyl]-4H-3,1-benzoxazin-4-one (25 mg, 0.06 mmol) in THF (1 mL). The reaction was stirred overnight at ambient temperature, concentrated to dryness and mixed with saturated aqueous NaHCO3 (1 mL) and CH2Cl2 (2 mL). The mixture was filtered through a plug of diatomaceous earth and treated with an isocyanate resin (methylisocyanate polystyrene HL, 0.360 mmol) overnight. Purification consisted of applying this mixture directly onto a column of silica and eluting with 1% MeOH in CHCl3.

Workup

  1. stirringThe reaction was stirred overnight at ambient temperature
  2. concentrationconcentrated to dryness
  3. additionmixed with saturated aqueous NaHCO3 (1 mL) and CH2Cl2 (2 mL)
  4. filtrationThe mixture was filtered through a plug of diatomaceous earth
  5. customPurification
  6. washeluting with 1% MeOH in CHCl3

Sources & evidence

ORD record
ord-be057b7cf6984a2a9573f9ccc2932313
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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