Ethyl iodoacetate → HCID 86610687, compound

HRID 506403Notes

Reaction equation

HRID 506403 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.[H-].[Na+].I[CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48]>CN(C)C=O>[F:40][C:37]([F:38])([F:39])[C:35]1[CH:34]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:41])[F:42])[CH:36]=1)[CH2:6][C:7]1[C:12]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]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)[N:23]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[C@H:22]([CH2:32][CH3:33])[CH2:21]2)[N:8]=1

Participants

5

Reactant 3

HCID 12183Ethyl iodoacetateHCID 24758Sodium hydrideHCID 86610671HCID 86610671, compound

Product 1

HCID 86610687HCID 86610687, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (300 mg) is dissolved in N,N-dimethylformamide (3 ml), and thereto is added sodium hydride (62.7%, 21 mg) under ice-cooling, then after 1 hour added ethyl iodoacetate (71 μl). The mixture is stirred at room temperature for 24 hours. The reaction solution is 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 NH-column chromatography (silica gel; hexane:ethyl acetate=9:1→4:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(morpholin-4-yl)pyrimidin-2-yl]}amino-1-ethoxycarbonylmethyl-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine (107 mg). MS (m/z): 683 [M+H]+.

Workup

  1. temperaturecooling
  2. customThe reaction solution is partitioned
  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 NH-column chromatography (silica gel; hexane:ethyl acetate=9:1→4:1)

Sources & evidence

ORD record
ord-6aea8685dda447a18f836d939cabdff5
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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