Triethylamine → HCID 86626767, compound

HRID 604009Notes

Reaction equation

HRID 604009 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[NH:34][CH2:35][CH3:36])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][N:9]=1.[CH2:46]([N:48]([CH2:51]C)CC)[CH3:47].ClC(Cl)([O:56]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[F:43][C:40]([F:41])([F:42])[C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:44])[F:45])[CH:39]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[N:34]([CH2:35][CH3:36])[C:51]([NH:48][CH2:46][CH3:47])=[O:56])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][N:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 86626761HCID 86626761, compound

Product 1

HCID 86626767HCID 86626767, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-ethylamino-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (200 mg) and triethylamine (51 μl) are dissolved in methylene chloride (1 ml), and thereto is added triphosgene (36 mg) in a small amount at room temperature. The reaction solution is stirred at room temperature for 10 minutes and concentrated under reduced pressure. The residue is dissolved in tetrahydrofuran (1 ml) and therero is added a 2M ethylamine in tetrahydrofuran (1 ml) and the mixture is stirred at room temperature for 30 minutes. To the reaction solution are added ethyl acetate and a 1N-hydrochloric acid, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→1:1) to give ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(1,3-diethylureido)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (181 mg). MS (m/z): 724 [M+H]+

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue is dissolved in tetrahydrofuran (1 ml)
  3. additionis added a 2M ethylamine in tetrahydrofuran (1 ml)
  4. stirringthe mixture is stirred at room temperature for 30 minutes
  5. additionTo the reaction solution are added ethyl acetate
  6. customa 1N-hydrochloric acid, and the mixture is separated
  7. washthe organic layer is washed with a saturated brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→1:1)

Sources & evidence

ORD record
ord-6ce58ce0fe2c4ff68aedb4b648e1b475
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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