2-(Chloromethyl)anisole → HCID 18654570, compound

HRID 2226032Notes

Reaction equation

HRID 2226032 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17](=[O:29])[N:18]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:13][C@H:12]2[C:30]([NH:32][CH2:33][CH2:34][NH:35][CH2:36][C:37](=[O:39])[NH2:38])=[O:31])=[O:10])[CH:5]=[CH:6][CH:7]=1.[CH3:46][O:47][C:48]1[CH:55]=[CH:54][CH:53]=[CH:52][C:49]=1[CH2:50]Cl.CCN(C(C)C)C(C)C>C(#N)C.C(Cl)(Cl)Cl>[CH2:24]([N:18]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:17]([N:14]1[CH2:15][CH2:16][N:11]([C:9](=[O:10])[N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C@H:12]([C:30]([NH:32][CH2:33][CH2:34][N:35]([CH2:50][C:49]2[CH:52]=[CH:53][CH:54]=[CH:55][C:48]=2[O:47][CH3:46])[CH2:36][C:37](=[O:39])[NH2:38])=[O:31])[CH2:13]1)=[O:29])[CH2:25][CH2:26][CH2:27][CH3:28]

Participants

6

Reactant 3

HCID 814952-(Chloromethyl)anisoleHCID 81531DiisopropylethylamineHCID 54517785HCID 54517785, compound

Product 1

HCID 18654570HCID 18654570, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 74 mg (ca. 0.11 mmole) of 1-(N-(3-chlorophenyl)-N-phenylcarbamoyl)-2-(2-(N-(methylcarboxamido)amino)-N-(methyl)ethylaminocarbonyl)- 4-(N,N-di-n-pentylcarbamoyl)piperazine (from Step E above) in 2 mL of acetonitrile was treated with 72 mg (0.23 mmole) of a 50 wt % solution of 2-methoxybenzyl chloride in chloroform and 60 microliters (0.35 mmole) of DIEA, and the mixture was stirred at room temperature for 24 hours and then at 80° C. for 36 hours. After cooling to room temperature, the mixture was concentrated in vacuo and the residue purified by flash chromatography on 23 g of silica gel eluting with 500 mL of 100:3:0.1 CH2Cl2 :methanol:ammonia water. Impure fractions containing product were resubmitted to the chromatographic conditions given above. The pooled product fractions were then purified by flash chromatography on 23 g of silica gel eluting with 700 mL of 100:2 CH2Cl2 :methanol and then 200 mL of 100:4 CH2Cl2 :methanol to provide 20 mg (23%) of an oil.

Workup

  1. waitat 80° C. for 36 hours
  2. temperatureAfter cooling to room temperature
  3. concentrationthe mixture was concentrated in vacuo
  4. customthe residue purified by flash chromatography on 23 g of silica gel eluting with 500 mL of 100:3:0.1 CH2Cl2
  5. additionImpure fractions containing product
  6. customThe pooled product fractions were then purified by flash chromatography on 23 g of silica gel eluting with 700 mL of 100:2 CH2Cl2

Sources & evidence

ORD record
ord-c32d24ebf89840739285334c85f8dd08
Source dataset
uspto-grants-1994_09
Patent number
US05344830

Reaction notes

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