Ammonium Chloride → (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(5-hydroxymethylpyridin-3-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

HRID 506365Notes

Reaction equation

HRID 506365 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]([C:40]3[CH:41]=[N:42][CH:43]=[C:44]([CH:46]=[O:47])[CH:45]=3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:48][CH3:49])=[O:5])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.O1CCCC1.[Cl-].[NH4+]>O1CCCC1>[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:37])([F:38])[F:39])[CH:29]=[C:30]([C:32]([F:33])([F:35])[F:34])[CH:31]=3)[C:22]([C:40]3[CH:41]=[N:42][CH:43]=[C:44]([CH2:46][OH:47])[CH:45]=3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:48][CH3:49])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 86597605diisobutylaluminium hydride THFHCID 86610596(2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(5-formylpyridin-3-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Product 1

HCID 86610597(2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(5-hydroxymethylpyridin-3-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(5-formylpyridin-3-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (118 mg) is dissolved in tetrahydrofuran (1.5 ml), then thereto is added 1M-diisobutylaluminum hydride-tetrahydrofuran solution (0.33 ml) dropwise under ice-cooling and the mixture is stirred for 1 hours under nitrogen flow under ice-cooling. A aqueous saturated ammonium chloride solution is added to the reaction mixture and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=1:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(5-hydroxymethylpyridin-3-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (84 mg). MS (m/z): 691 [M+H]+

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed with a 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=1:1)

Sources & evidence

ORD record
ord-29b29e3ad5b346248b3ec99a98b77285
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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