Diisopropylethylamine → Methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate

HRID 2075220Notes

Reaction equation

HRID 2075220 reaction equation
[CH2:1]([C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10](I)[CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]([C:18]1[CH:32]=[CH:31][C:21]([CH2:22][N:23]2[CH2:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24]2)=[CH:20][C:19]=1[F:33])#[CH:17].C(N(C(C)C)C(C)C)C>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH2:1]([C:8]1[CH:9]=[C:10]2[C:11](=[CH:12][CH:13]=1)[NH:14][C:16]([C:18]1[CH:32]=[CH:31][C:21]([CH2:22][N:23]3[CH2:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24]3)=[CH:20][C:19]=1[F:33])=[CH:17]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 25254788Methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylateHCID 584153354-Benzyl-2-iodobenzenamine

Product 1

HCID 58415313Methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a sealed flask was added 4-benzyl-2-iodobenzenamine (0.20 g, 0.65 mmol) and methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate (0.32 g, 1.3 mmol) in THF (15 mL). To this solution was added PdCl2(PPh3)2 (0.045 g, 0.065 mmol), CuI (0.025 g, 0.13 mmol), and ethyldiisopropylamine (0.90 mL, 5.2 mmol). The flask was flushed with Ar, sealed and placed in a preheated oil bath at 100° C. for 3 h. The mixture was concentrated under reduced pressure to afford a dark oil which was adsorbed onto silica and purified (30% EtOAc/hexanes to 100% EtOAc) to afford title compound as a yellow oil. MS (ESI) m/z: Calculated: 428.1; Observed: 429.1 (M++1).

Workup

  1. customThe flask was flushed with Ar
  2. customsealed
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customto afford a dark oil which
  5. custompurified (30% EtOAc/hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-1616b9075f354d90a38f8a7e4799d686
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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