proline dl-form → HCID 59369340, compound

HRID 1689793Notes

Reaction equation

HRID 1689793 reaction equation
Cl.[CH:2]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[CH2:18][O:19][CH:20]2[CH2:26][CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH2:4][CH2:3]1.[CH3:27][O:28][C:29]([C:31]1[C:39]2[C:34](=[CH:35][C:36](Br)=[CH:37][CH:38]=2)[N:33]([CH3:41])[CH:32]=1)=[O:30].N1CCCC1C(O)=O.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>CS(C)=O.[Cu]I>[CH3:27][O:28][C:29]([C:31]1[C:39]2[C:34](=[CH:35][C:36]([N:23]3[CH2:24][CH2:25][CH2:26][CH:20]([O:19][CH2:18][C:6]4[C:7]([C:10]5[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=5[Cl:16])=[N:8][O:9][C:5]=4[CH:2]4[CH2:3][CH2:4]4)[CH2:21][CH2:22]3)=[CH:37][CH:38]=2)[N:33]([CH3:41])[CH:32]=1)=[O:30]

Participants

8

Reactant 5

HCID 614proline dl-formHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 57443279Methyl 6-bromo-1-methyl-1H-indole-3-carboxylateHCID 669061074-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepane hydrochloride

Product 1

HCID 59369340HCID 59369340, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepane hydrochloride (298 mg, 0.713 mmol), 6-bromo-1-methyl-1H-indole-3-carboxylic acid methyl ester (195 mg, 0.727 mmol), copper (I) iodide (40 mg, 0.208 mmol), DL-proline (60 mg, 0.516 mmol), and potassium carbonate (385 mg, 2.79 mmol) in dimethyl sulfoxide (3 mL) is heated to 100° C. for 18 h under nitrogen atmosphere. Saturated aqueous ammonium chloride is added and the mixture is extracted with ethyl acetate (3×). The combined ethyl acetate layers are washed with water (2×), brine (3×), dried (MgSO4), and concentrated under reduced pressure. The residue is purified via flash chromatography (40 g silica) using a gradient of ethyl acetate in heptane (0 to 70%) to provided the title compound (47 mg, 12%). LC-ES/MS m/z 569.0 (M+1).

Workup

  1. extractionthe mixture is extracted with ethyl acetate (3×)
  2. washThe combined ethyl acetate layers are washed with water (2×), brine (3×)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified via flash chromatography (40 g silica)

Sources & evidence

ORD record
ord-a56d82bccc604b3890c2233e739c5d3d
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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