Water → HCID 18706969, compound

HRID 1422102Notes

Reaction equation

HRID 1422102 reaction equation
[CH2:1]([C:3]1[C:11]2[N:6]3[C:7](=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)=[CH:16][CH:15]=4)[CH:13]=[C:5]3[C:4]=1[C:29]1[CH:34]=[CH:33][C:32]([O:35]C)=[CH:31][CH:30]=1)[CH:8]=[CH:9][CH:10]=2)[CH3:2].Cl.[NH+]1C=CC=CC=1.O.C(=O)([O-])O.[Na+]>CO.ClCCl>[CH2:1]([C:3]1[C:11]2[N:6]3[C:7](=[C:12]([C:14]4[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][N:23]5[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]5)=[CH:18][CH:19]=4)[CH:13]=[C:5]3[C:4]=1[C:29]1[CH:30]=[CH:31][C:32]([OH:35])=[CH:33][CH:34]=1)[CH:8]=[CH:9][CH:10]=2)[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 18706979HCID 18706979, compoundHCID 21584435Pyridinium hydrochloride

Product 1

HCID 18706969HCID 18706969, compoundYield 29.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

1-Ethyl-2-(4-methoxyphenyl)-4-[4-(2-piperidinoethoxy)phenyl]pyrrolo[2,1,5-cd]indolizine (190 mg, 0.4 mmol) and pyridinium hydrochloride (462 mg, 4.0 mmol) was melted together at 170° C., and stirring was continued for 24 hours at 170° C. The mixture was cooled to room temperature and dissolved in 10 ml of methanol and 50 ml of dichloromethane. 100 ml of water and solid sodium hydrogen carbonate was added until pH=8. The aqueous layer was extracted with 10% of methanol in dichloromethane (2×50 ml), and the combined organic layers were washed with brine, dried oversodium sulfate and evaporated. The crude product was purified by column chromatography over silica gel 60, using 10% of methanol in dichloromethane as the eluent. The crude product was recrystallized from methanol, dichloromethane and petroleum ether to afford 55 mg (29%) of 1-ethyl-2-(4-hydroxyphenyl)-4-[4-(2-piperidinoethoxy)phenyl]pyrrolo[2,1,5-cd]indolizine. MS(SP): m/z 464 (M+). 1H--NMR (DMSO-d6, 200 MHz) δ: 1.31-1.58 (m,9 H); 2.39-2.49 (m, 4 H); 2.68 (t, 2 H); 3.22 (q, 2 H); 4.12 (t, 2 H); 7.00 (d, 2 H); 7.07 (d, 2 H); 7.66-7.79 (m, 3 H); 7.83-7.98 (m, 3 H); 8.11 (d, 1 H); 8.29 (d, 1 H); 9.83 (br s, 1 H).

Workup

  1. customwas melted together at 170° C.
  2. extractionThe aqueous layer was extracted with 10% of methanol in dichloromethane (2×50 ml)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried oversodium sulfate
  5. customevaporated
  6. customThe crude product was purified by column chromatography over silica gel 60
  7. customThe crude product was recrystallized from methanol, dichloromethane and petroleum ether

Sources & evidence

ORD record
ord-353eaeaf06474745bc48e2e422d90eb2
Source dataset
uspto-grants-2000_06
Patent number
US06080754

Reaction notes

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