Methanol → HCID 21073875, compound

HRID 1373620Notes

Reaction equation

HRID 1373620 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:11])([CH3:10])[CH3:9])=[CH:6][CH:5]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=3[Cl:30])[CH2:19][CH2:18]2)[N:3]=1.CCN(CC)CC.[C:38](Cl)(Cl)=[O:39].CO>C1COCC1.C1(C)C=CC=CC=1>[Cl:30][C:24]1[C:25]([Cl:29])=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:4]2[CH:5]=[CH:6][C:7]3[C:8]([CH3:10])([CH3:9])[O:11][C:38](=[O:39])[NH:1][C:2]=3[N:3]=2)[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 887MethanolHCID 6371PhosgeneHCID 8471TriethylamineHCID 21073206HCID 21073206, compound

Product 1

HCID 21073875HCID 21073875, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(2-amino-6-{5-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-pentyl}-pyridin-3-yl)-propan-2-ol (442 mg, 0.98 mmol) in THF (4 mL) and toluene (1 mL) was added Et3N (0.30 mL, 2.15 mmol, 2.2 equiv). The mixture was cooled to 0° C. and phosgene (20% in toluene, 0.65 mL, 1.3 mmol) was added. A precipitate formed. The reaction was stirred at 0° C. for 15 min and at room temperature for 2 h. MeOH was added to quench the excess phosgene. Saturated NaHCO3 and H2O were added and the mixture was extracted with EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4 and concentrated. Purification by liquid chromatography (3.5% MeOH/CH2Cl2) gave the title compound as a white foam (411 mg, 0.861 mmol, 88%). The foam was dissolved in Et2O/CH2Cl2 and 1 M HCl in Et2O (0.86 mL) was added. The resulting white precipitate was collected by filtration, washed with Et2O and dried to give a fluffy white solid (400 mg). MS: APCI: M+1: 477.1 (Exact Mass: 476.17).

Workup

  1. customA precipitate formed
  2. customto quench the excess phosgene
  3. additionSaturated NaHCO3 and H2O were added
  4. extractionthe mixture was extracted with EtOAc
  5. washThe organic layer was washed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by liquid chromatography (3.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-457b473ee54a4b7293e8ee997ba0b353
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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