Dichloromethane → HCID 67190457, compound

HRID 551821Notes

Reaction equation

HRID 551821 reaction equation
[N:1]1([C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([O:20][CH3:21])[CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH2:3][CH2:2]1.Cl[CH2:23]Cl.ClC(Cl)(O[C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.Cl.Cl.[NH:39]1[CH2:43][CH2:42][CH:41]([C:44]2[CH:45]=[N:46][NH:47][CH:48]=2)[CH2:40]1>C(N(CC)CC)C>[CH3:23][O:16][C:15](=[O:17])[C:14]1[CH:18]=[CH:19][C:11]([N:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([C:29]([N:39]3[CH2:43][CH2:42][CH:41]([C:44]4[CH:45]=[N:46][NH:47][CH:48]=4)[CH2:40]3)=[O:35])[CH2:3][CH2:2]2)=[CH:12][C:13]=1[O:20][CH3:21]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 94429TriphosgeneHCID 67186545HCID 67186545, compoundHCID 671872291000688-81-2

Product 1

HCID 67190457HCID 67190457, compound

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

0.92 g of the methyl ester of 4-(3,4-dihydro-2H-quinoxalin-1-yl)-2-methoxybenzoic acid and 15 ml of dichloromethane are introduced into a three-necked flask equipped with a magnetic stirrer and placed under an inert atmosphere. After cooling to +4° C., 1.92 ml of triethylamine and 0.33 g of triphosgene are successively added. The reaction medium is stirred at ambient temperature for 3 h. 0.64 g of 4-pyrrolidin-3-yl-1H-pyrazole dihydrochloride is then introduced and the mixture is stirred at ambient temperature for 18 h. The reaction medium is washed with a saturated aqueous sodium hydrogencarbonate solution; the organic phase is dried over sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel eluted with a gradient of methanol from 2% to 4% in dichloromethane. The product obtained is rechromatographed on silica gel eluted with a dichloromethane/methanol 99/1 to 92/8 gradient. 1.06 g of 2-methoxy-4-{4-[3-(1H-pyrazol-4-yl)pyrrolidine-1-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}benzoic acid methyl ester are obtained.

Workup

  1. customequipped with a magnetic stirrer
  2. temperatureAfter cooling to +4° C.
  3. stirringthe mixture is stirred at ambient temperature for 18 h
  4. washThe reaction medium is washed with a saturated aqueous sodium hydrogencarbonate solution
  5. dry with materialthe organic phase is dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is chromatographed on silica gel
  8. washeluted with a gradient of methanol from 2% to 4% in dichloromethane
  9. customThe product obtained
  10. customis rechromatographed on silica gel
  11. washeluted with a dichloromethane/methanol 99/1 to 92/8 gradient

Sources & evidence

ORD record
ord-8f291cb43f7240bda6e390a8453cf1cf
Source dataset
uspto-grants-2011_05
Patent number
US07947834B2

Reaction notes

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