Triethylamine → 2-(4-(4-((2-Amino-5-pyrimidinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972468

Reaction equation

HRID 1972468 reaction equation
Cl.Cl.[F:3][C:4]([F:24])([F:23])[C:5]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1)([OH:10])[C:6]([F:9])([F:8])[F:7].C([N:27](CC)CC)C.Cl[C:33]1[N:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][N:34]=1>C(Cl)Cl>[NH2:27][C:33]1[N:38]=[CH:37][C:36]([S:39]([N:20]2[CH2:21][CH2:22][N:17]([C:14]3[CH:13]=[CH:12][C:11]([C:5]([OH:10])([C:6]([F:9])([F:8])[F:7])[C:4]([F:3])([F:23])[F:24])=[CH:16][CH:15]=3)[CH2:18][CH2:19]2)(=[O:41])=[O:40])=[CH:35][N:34]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 432443662-Chloropyrimidine-5-sulfonyl chlorideHCID 866703461,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride

Product 1

HCID 763285842-(4-(4-((2-Amino-5-pyrimidinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 40.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 100-mL round-bottomed flask was charged with 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (0.45 g, 1.13 mmol, Example 91), 10 mL of CH2Cl2, triethylamine (0.63 mL, 4.51 mmol), and 2-chloro-5-pyrimidinesulfonyl chloride (0.24 g, 1.13 mmol, Matrix Scientific, Columbia, S.C.). After stirring for 15 min at room temperature, the mixture was concentrated then diluted with 10 mL of EtOH and 10 mL of NH4OH. The mixture was stirred at room temperature for an additional 1 h and then diluted with EtOAc. The organics were separated, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography on silica gel (0 to 65% EtOAc in hexanes) to give 2-(4-(4-((2-amino-5-pyrimidinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.22 g). 1H NMR (400 MHz, CD3OD) δ=8.58 (s, 2H), 7.57 (d, J=8.8 Hz, 2H), 7.03 (d, J=9.2 Hz, 2H), 3.38-3.34 (m, 4H), 3.22-3.17 (m, 4H). m/z (ESI, +ve ion) 485.6 (M+H)+. GK-GKRP IC50 (Binding)=0.258 μM; GK-GKRP EC50 (LC MS/MS-2)=0.518 μM.

Workup

  1. concentrationthe mixture was concentrated
  2. additionthen diluted with 10 mL of EtOH and 10 mL of NH4OH
  3. stirringThe mixture was stirred at room temperature for an additional 1 h
  4. additiondiluted with EtOAc
  5. customThe organics were separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (0 to 65% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6c60364c59ab4b2aa08be04e2320bdb3
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Linked notes

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