Sodium Carbonate → HCID 178473239, compound

HRID 506390Notes

Reaction equation

HRID 506390 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]([CH2:40][CH2:41][C:42]#[N:43])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:44][CH3:45])=[O:5])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].Cl.[NH2:53][OH:54]>C(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: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)[C:22]([CH2:40][CH2:41][C:42](=[NH:43])[NH:53][OH:54])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:44][CH3:45])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 86610591HCID 86610591, compound

Product 1

HCID 178473239HCID 178473239, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-[5-(2-cyanoethyl)-pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (500 mg) is dissolved in ethanol (5 ml), and thereto are added sodium carbonate (292 mg) and hydroxylamine hydrochloride (192 mg). The mixture is heated at 80° C. and stirred for 31.5 hours. The reaction solution is cooled to room temperature, and partitioned by adding water and ethyl acetate. The organic layer is washed with saturated brine, then dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→19:1) to give (2R,4S)-4-([3,5-bis(trifluoromethyl)benzyl]-{5-[2-(N-hydroxycarbamimidoyl)ethyl]pyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (297 mg) MS (m/z): 670 [M+H]+, and (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(2-carbamoylethyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (140 mg) MS (m/z): 655 [M+H]+.

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. custompartitioned
  3. additionby adding water and ethyl acetate
  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; chloroform:methanol=1:0→19:1)

Sources & evidence

ORD record
ord-011a3727eb3b4718926ec0746c79aa16
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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