Triethylamine → HCID 86610634, compound

HRID 506387Notes

Reaction equation

HRID 506387 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([OH:40])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].[CH3:43][O:44][C:45]([C:47]1[CH:52]=[CH:51][C:50](B(O)O)=[CH:49][CH:48]=1)=[O:46].C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:38])([F:39])[F:37])[CH:27]=3)[C:22]([O:40][C:50]3[CH:51]=[CH:52][C:47]([C:45]([O:44][CH3:43])=[O:46])=[CH:48][CH:49]=3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27343694-Methoxycarbonylphenylboronic acidHCID 86610574(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Product 1

HCID 86610634HCID 86610634, compoundYield 63.5%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

(2R,4S)-4-{[3, 5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (170 mg) is dissolved in methylene chloride (3 ml), and thereto are added 4-methoxycarbonylphenylboronic acid (51 mg), copper (II) acetate (52 mg), triethylamine (79 μl) and molecular sieves 4A (170 mg). The mixture is stirred overnight at room temperature. The insoluble materials are removed by filtration and the filtrate is partitioned by adding ethyl acetate and saturated brine. The organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→3:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(4-methoxycarbonylphenoxy)-pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (132 mg). MS (m/z): 734 [M+H]+.

Workup

  1. customThe insoluble materials are removed by filtration
  2. customthe filtrate is partitioned
  3. additionby adding ethyl acetate and saturated brine
  4. washThe organic layer is washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→3:1)

Sources & evidence

ORD record
ord-2ae55810c5974c6ab528b7d5f558966e
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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