1,2-Dichloroethane → HCID 44434945, compound

HRID 130694Notes

Reaction equation

HRID 130694 reaction equation
ClC(OC(Cl)=O)C.C([N:15]([CH2:34][CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:16][CH2:17][C:18]1[CH:33]=[CH:32][C:21]([O:22][C:23]2[CH:31]=[CH:30][C:26]([C:27]([NH2:29])=[O:28])=[CH:25][N:24]=2)=[CH:20][CH:19]=1)C1C=CC=CC=1.ClCCCl.N>CO>[C:37]1([CH2:36][CH2:35][CH2:34][NH:15][CH2:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([NH2:29])=[O:28])=[CH:25][N:24]=3)=[CH:32][CH:33]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 222AmmoniaHCID 5213051-Chloroethyl chloroformateHCID 68746129HCID 68746129, compound

Product 1

HCID 44434945HCID 44434945, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Add 1-chloroethylchloroformate (0.056 mL, 0.52 mmol) to a stirred solution of 6-(4-{2-[benzyl-(3-phenyl-propyl)-amino]-ethyl}-phenoxy)-nicotinamide (0.1211 g, 0.2603 mmol) (Example 3) and 1,2-dichloroethane (5 mL). Beat the reaction to reflux under nitrogen for 1.5 h. Add methanol (7 mL) and heat at reflux under nitrogen for 1 h. Cool the reaction to room temperature and add 2 M ammonia in methanol (5 mL). Concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 1% concentrated ammonium hydroxide/10% ethanol/chloroform to yield 0.0654 g (67%) of 6-{4-[2-(3-phenyl-propylamino)-ethyl]-phenoxy}-nicotinamide: HPLC (30/70 to 90/10 ACN/(0.1% TFA in water) Zorbax SB-Phenyl Column 4.6 mm×15 cm×5 micron: Retention time: 7.48 minutes, Purity: 99.2%; mass spectrum (ion spray): m/z=376.2 (M+1).

Workup

  1. customthe reaction
  2. temperatureto reflux under nitrogen for 1.5 h
  3. temperatureat reflux under nitrogen for 1 h
  4. temperatureCool
  5. customthe reaction to room temperature
  6. concentrationConcentrate on a rotary evaporator
  7. customto give the crude product
  8. customThe crude product is purified by flash chromatography on silica gel eluting with 1% concentrated ammonium hydroxide/10% ethanol/chloroform

Sources & evidence

ORD record
ord-5c0d7277bbc8403fbd206cc71201e805
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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