Diisopropylamine → N-methoxy-N-methyl-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-carboxamide

HRID 1064726Notes

Reaction equation

HRID 1064726 reaction equation
[OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])=[CH:4][C:3]=1I.[CH2:15]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH3:24])[CH2:16][C:17]#[CH:18].CC1C=CC(P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C(NC(C)C)(C)C>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[CH3:11][O:10][N:8]([CH3:9])[C:6]([C:5]1[CH:12]=[CH:13][C:2]2[O:1][C:17]([CH2:16][CH2:15][N:19]3[CH2:23][CH2:22][CH2:21][C@H:20]3[CH3:24])=[CH:18][C:3]=2[CH:4]=1)=[O:7]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 13956Phosphine, tris(4-methylphenyl)-HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 117712104-hydroxy-3-iodo-N-methoxy-N-methylbenzamide

Product 1

HCID 11438480N-methoxy-N-methyl-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-carboxamideYield 10.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

The product from Example 71D (11.6 g, 37.77 mmol) in acetonitrile (50 mL) was treated sequentially with a 0.12M solution of the product from Example 68B (378 mL, 45.33 mmol), Pd(OAc)2 (0.254 g, 1.13 mmol), tris(4-methylphenyl)phosphine (0.518 g, 1.699 mmol), and diisopropyl amine (39.7 mL, 283.3 mmol). After stirring at 25° C. for 10 minutes, the mixture was treated with copper iodide (2.158 g, 11.33 mmol) and heated at 50° C. in an inert atmosphere for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified on silica gel using 95% DCM, 9.9% MeOH, 0.1% NH4OH to provide the title compound (1.22 g, 10.2% yield). 1HNMR (300 MHz, CD3OD) δ 1.18 (d, 3H, J=6.1 Hz), 1.47 (m, 1H), 1.78 (m, 2H), 1.91-2.34 (m, 2H), 2.50 (m, 2H) 3.06 (m, 2H), 3.26 (m, 2H), 3.38 (s, 3H), 3.59 (s, 3H), 6.63 (s, 1H), 7.51 (q, 2H), 7.84 (1H); MS (ESI) m/z 317.2 (M+H)+.

Workup

  1. temperatureheated at 50° C. in an inert atmosphere for 18 hours
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified on silica gel using 95% DCM, 9.9% MeOH, 0.1% NH4OH

Sources & evidence

ORD record
ord-8c74c9187d1640b2baa459d31077ed58
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Reaction notes

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