p-(1-Piperazinyl)phenol → HCID 68438970, compound

HRID 1805978Notes

Reaction equation

HRID 1805978 reaction equation
[CH2:1]([O:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[NH:14][C:15]1[C:16]2[S:24][CH2:23][CH2:22][C:17]=2[N:18]=[C:19](Cl)[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1>O1CCOCC1>[CH2:1]([O:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[NH:14][C:15]1[C:16]2[S:24][CH2:23][CH2:22][C:17]=2[N:18]=[C:19]([N:35]2[CH2:36][CH2:37][N:32]([C:29]3[CH:30]=[CH:31][CH:26]=[CH:27][CH:28]=3)[CH2:33][CH2:34]2)[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 92467p-(1-Piperazinyl)phenolHCID 86616265HCID 86616265, compound

Product 1

HCID 68438970HCID 68438970, compoundYield 92.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

0.450 g (1.2 mmol) of ((1R,2R)-2-benzyloxycyclopentyl)(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amine (chiral) (VIII) and 0.760 mL (5.0 mmol) of 1-phenylpiperazine (III) are placed in 5 mL of dioxane, then reacted for 1 hour at 160° C. in the microwave. The reaction mixture is concentrated by evaporation, and the residue is combined with water and extracted with dichloromethane. The organic phase is separated off using a phase separator and evaporated to dryness. The crude product I is purified by chromatography through a 100 g silica gel cartridge with a solvent mixture of petroleum ether/ethyl acetate 8/2. 0.540 g of the product (89%) is obtained (m.p. 100° C.-105° C.). 1H NMR (400 MHz, DMSO): 7.36-7.18 (7H, m); 6.91 (2H, d); 6.79 (1H, t); 6.39 (1H, d); 4.59-4.40 (3H, m); 3.95-3.89 (1H, m); 3.79-3.69 (4H, m); 3.23 (2H, t); 3.11-3.03 (4H, m); 2.99 (2H, t); 2.11-2.00 (1H, m); 1.93-1.79 (1H, m); 1.77-1.50 (4H, m).

Workup

  1. customreacted for 1 hour at 160° C. in the microwave
  2. concentrationThe reaction mixture is concentrated by evaporation
  3. extractionextracted with dichloromethane
  4. customThe organic phase is separated off
  5. customevaporated to dryness
  6. customThe crude product I is purified by chromatography through a 100 g silica gel cartridge with a solvent mixture of petroleum ether/ethyl acetate 8/2

Sources & evidence

ORD record
ord-61a9ad154bf84e9f93470490ff65babe
Source dataset
uspto-grants-2013_01
Patent number
US08354531B2

Reaction notes

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