2-Chloroethyl isocyanate → HCID 86610683, compound

HRID 506401Notes

Reaction equation

HRID 506401 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:6][C:7]1[C:12]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:11][N:10]=[C:9]([NH:19][C@@H:20]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([O:30][CH3:31])[N:28]=3)[NH:23][C@H:22]([CH2:32][CH3:33])[CH2:21]2)[N:8]=1.[Cl:43][CH2:44][CH2:45][N:46]=[C:47]=[O:48].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[Cl:43][CH2:44][CH2:45][NH:46][C:47]([N:23]1[C:24]2[C:29](=[N:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C@@H:20]([NH:19][C:9]2[N:8]=[C:7]([CH2:6][C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:41])[F:42])[CH:36]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:34]=3)[C:12]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[CH:11][N:10]=2)[CH2:21][C@H:22]1[CH2:32][CH3:33])=[O:48]

Participants

5

Reactant 3

HCID 160352-Chloroethyl isocyanateHCID 516892Sodium BicarbonateHCID 86610671HCID 86610671, compound

Product 1

HCID 86610683HCID 86610683, compoundYield 90.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-[5-(morpholin-4-yl)-pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-1,2,3,4-tetrahydro-[1,5]naphthyridine (150 mg) is dissolved in toluene (2.0 ml), and thereto is added 2-chloroethyl isocyanate (40 mg). The mixture is stirred at 60° C. for 9 hours under nitrogen flow. To the reaction mixture is added a saturated aqueous sodium hydrogen carbonate solution, the mixture is extracted with ethyl acetate. 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=2:1→1:9) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)-benzyl]-[5-(morpholin-4-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid (2-chloroethyl)amide (160 mg). MS (m/z): 702/704 [M+H]+.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic layer is washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=2:1→1:9)

Sources & evidence

ORD record
ord-e32e0c9ec52c4313a52704d3b0374843
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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