Water → HCID 136387034, compound

HRID 506405Notes

Reaction equation

HRID 506405 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[C:24]([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)=[CH:23][C:22]([C:40](=[NH:43])[NH:41][OH:42])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:44][CH3:45])=[O:5])[CH3:2].C(N(CC)CC)C.Cl[C:54](Cl)([O:56]C(=O)OC(Cl)(Cl)Cl)Cl.O>ClCCl>[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[C:24]([CH2:25][C:26]3[CH:27]=[C:28]([C:36]([F:39])([F:37])[F:38])[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=3)=[CH:23][C:22]([C:40]3[NH:43][C:54](=[O:56])[O:42][N:41]=3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:44][CH3:45])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 94429TriphosgeneHCID 178473240HCID 178473240, compound

Product 1

HCID 136387034HCID 136387034, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-[5-(N-hydroxy-carbamimidoyl)pyridin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (193 mg) and triethylamine (126 μl) are dissolved in dichloromethane (3 ml), and thereto is added triphosgene (268 mg) at 0° C. The mixture is stirred at room temperature for 30 minutes. To the reaction solution are added water and dichloromethane, and the organic layer is washed with saturated brine. Then the organic layer is dried over sodium sulfate, and then concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→97:3) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)pyridin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (33 mg). MS (m/z): 667 [M+H]+.

Workup

  1. washthe organic layer is washed with saturated brine
  2. dry with materialThen the organic layer is dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→97:3)

Sources & evidence

ORD record
ord-bec3d9b7ab05478cbd54d604db63e40d
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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